Achondroplasia - A Bibliography and Dictionary for Physicians, Patients, and Genome Researchers

ACHONDROPLASIA

3-in-1

Medical

Reference

A Bibliography and Dictionary for Physicians, Patients, and Genome Researchers TO INTERNET REFERENCES

ACHONDROPLASIA A BIBLIOGRAPHY AND DICTIONARY FOR PHYSICIANS, PATIENTS, AND GENOME RESEARCHERS

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

ICON Health Publications ICON Group International, Inc. 7404 Trade Street San Diego, CA 92121 USA Copyright ©2007 by ICON Group International, Inc. Copyright ©2007 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher’s note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circ*mstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Achondroplasia: A Bibliography and Dictionary for Physicians, Patients, and Genome Researchers/ James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-11318-X 1. Achondroplasia-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsem*nt, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [emailprotected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International, Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on achondroplasia. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Chaired Professor of Management Science at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 7404 Trade Street San Diego, CA 92121 USA Fax: 858-635-9414 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON ACHONDROPLASIA ................................................................................... 3 Overview........................................................................................................................................ 3 Genetics Home Reference ............................................................................................................... 3 What Is Achondroplasia?............................................................................................................... 3 How Common Is Achondroplasia? ................................................................................................ 4 What Genes Are Related to Achondroplasia? ................................................................................ 4 How Do People Inherit Achondroplasia?....................................................................................... 4 Where Can I Find Additional Information about Achondroplasia?............................................... 4 References....................................................................................................................................... 6 What Is the Official Name of the FGFR3 Gene?............................................................................ 7 What Is the Normal Function of the FGFR3 Gene? ...................................................................... 7 What Conditions Are Related to the FGFR3 Gene? ...................................................................... 8 Where Is the FGFR3 Gene Located? .............................................................................................. 9 References..................................................................................................................................... 10 Federally Funded Research on Achondroplasia............................................................................ 11 The National Library of Medicine: PubMed ................................................................................ 18 CHAPTER 2. ALTERNATIVE MEDICINE AND ACHONDROPLASIA ................................................... 62 Overview...................................................................................................................................... 62 National Center for Complementary and Alternative Medicine.................................................. 62 Additional Web Resources ........................................................................................................... 63 General References ....................................................................................................................... 64 APPENDIX A. HELP ME UNDERSTAND GENETICS ......................................................................... 66 Overview...................................................................................................................................... 66 The Basics: Genes and How They Work....................................................................................... 66 Genetic Mutations and Health..................................................................................................... 77 Inheriting Genetic Conditions ..................................................................................................... 83 Genetic Consultation ................................................................................................................... 91 Genetic Testing ............................................................................................................................ 93 Gene Therapy ............................................................................................................................... 99 The Human Genome Project and Genomic Research................................................................. 102 APPENDIX B. PHYSICIAN RESOURCES ........................................................................................... 105 Overview.................................................................................................................................... 105 NIH Guidelines.......................................................................................................................... 105 NIH Databases........................................................................................................................... 106 Other Commercial Databases..................................................................................................... 109 APPENDIX C. PATIENT RESOURCES .............................................................................................. 110 Overview.................................................................................................................................... 110 Patient Guideline Sources.......................................................................................................... 110 Finding Associations.................................................................................................................. 112 Resources for Patients and Families........................................................................................... 113 ONLINE GLOSSARIES................................................................................................................ 115 Online Dictionary Directories ................................................................................................... 116 ACHONDROPLASIA DICTIONARY ....................................................................................... 118 INDEX .............................................................................................................................................. 154

FORWARD In March 2001, the National Institutes of Health issued the following warning: “The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading.”1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with achondroplasia is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about achondroplasia, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to achondroplasia, from the essentials to the most advanced areas of research. Special attention has been paid to present the genetic basis and pattern of inheritance of achondroplasia. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on achondroplasia. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to achondroplasia, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. We hope these resources will prove useful to the widest possible audience seeking information on achondroplasia. The Editors

From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/.

CHAPTER 1. STUDIES ON ACHONDROPLASIA Overview In this chapter, we will show you how to locate peer-reviewed references and studies on achondroplasia. For those interested in basic information about achondroplasia, we begin with a condition summary published by the National Library of Medicine.

Genetics Home Reference Genetics Home Reference (GHR) is the National Library of Medicine’s Web site for consumer information about genetic conditions and the genes or chromosomes responsible for those conditions. Here you can find a condition summary on achondroplasia that describes the major features of the condition, provides information about the condition’s genetic basis, and explains its pattern of inheritance. In addition, a summary of the gene or chromosome related to achondroplasia is provided. 2 The Genetics Home Reference has recently published the following summary for achondroplasia:

What Is Achondroplasia?3 Achondroplasia is a disorder of bone growth. Although achondroplasia literally means "without cartilage formation," the problem is not in forming cartilage but in converting it to bone, particularly in the long bones of the arms and legs. All people with achondroplasia have short stature. The average height of an adult male with achondroplasia is 131 centimeters (4 feet, 4 inches), and the average height for adult females is 124 centimeters (4 feet, 1 inch). Characteristic features of achondroplasia include an average-size trunk, short arms and legs with particularly short upper arms and thighs, 2 3

This section has been adapted from the National Library of Medicine: http://ghr.nlm.nih.gov/.

Adapted from the Genetics Home Reference of the National Library of Medicine: http://ghr.nlm.nih.gov/condition=achondroplasia.

Achondroplasia

limited range of motion at the elbows, and an enlarged head (macrocephaly) with a prominent forehead. Fingers are typically short and the ring finger and middle finger may diverge, giving the hand a three-pronged (trident) appearance. People with achondroplasia are generally of normal intelligence. Health problems commonly associated with achondroplasia include episodes in which breathing slows or stops for short periods (apnea), obesity, and recurrent ear infections. In adulthood, individuals with the condition usually develop a pronounced and permanent sway of the lower back (lordosis) and bowed legs. Older individuals often have back pain, which can cause difficulty with walking.

How Common Is Achondroplasia? Achondroplasia is the most common type of short-limbed dwarfism. The condition occurs in 1 in 15,000 to 40,000 newborns.

What Genes Are Related to Achondroplasia? Mutations in the FGFR3 (http://ghr.nlm.nih.gov/gene=fgfr3) gene cause achondroplasia. The FGFR3 gene provides instructions for making a protein that is involved in the development and maintenance of bone and brain tissue. This protein limits the formation of bone from cartilage (a process called ossification), particularly in the long bones. Two specific mutations in the FGFR3 gene are responsible for almost all cases of achondroplasia. Researchers believe that these mutations cause the protein to be overly active, which interferes with skeletal development and leads to the disturbances in bone growth seen with this disorder.

How Do People Inherit Achondroplasia? Achondroplasia is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. About 80 percent of people with achondroplasia have average-size parents; these cases result from a new mutation in the FGFR3 gene. In the remaining cases, people with achondroplasia have inherited an altered FGFR3 gene from one or two affected parents. Individuals who inherit two altered copies of this gene typically have very severe problems with bone growth, and are usually stillborn or die shortly after birth from respiratory failure.

Where Can I Find Additional Information about Achondroplasia? You may find the following resources about achondroplasia helpful. These materials are written for the general public.

Studies

NIH Publications - National Institutes of Health •

http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gnd.section.256 MedlinePlus - Health Information

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Encyclopedia: Achondroplasia: http://www.nlm.nih.gov/medlineplus/ency/article/001577.htm

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Encyclopedia: Lordosis: http://www.nlm.nih.gov/medlineplus/ency/article/003278.htm

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Health Topic: Dwarfism: http://www.nlm.nih.gov/medlineplus/dwarfism.html Educational Resources - Information Pages

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Ask the Geneticist: Inheritance of achondroplasia: http://www.askthegen.org/question.php?question_id=692

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Centre for Genetics Education: http://www.genetics.com.au/factsheet/43.htm

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Children's Hospital Boston: http://www.childrenshospital.org/az/Site558/mainpageS558P0.html

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Department of Orthopaedic Surgery, Johns Hopkins University: http://www.hopkinsmedicine.org/orthopedicsurgery/achondroplasia.html

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Greenberg Center for Skeletal Dysplasias: http://www.hopkinsmedicine.org/greenbergcenter/achon.htm

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Madisons Foundation: http://www.madisonsfoundation.org/content/3/1/display.asp?did=260

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Nemours: http://www.nemours.org/internet?url=no/dysplasia/achondroplasia.html

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Orphanet: http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=15

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The Wellcome Trust: http://genome.wellcome.ac.uk/doc_WTD020861.html

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University of Virginia Health System: http://www.healthsystem.virginia.edu/UVAHealth/peds_diabetes/achondro.cfm Patient Support - for Patients and Families

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Human Growth Foundation: http://www.hgfound.org

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International Skeletal Dysplasia Registry, Cedars-Sinai Medical Center: http://www.csmc.edu/3805.html

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Little People of America, Inc.: http://www.lpaonline.org

Achondroplasia

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March of Dimes: http://www.marchofdimes.com/pnhec/4439_1204.asp

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National Organization for Rare Disorders: http://www.rarediseases.org/search/rdbdetail_abstract.html?disname=Achondroplasia

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Resource list from the University of Kansas Medical Center: http://www.kumc.edu/gec/support/dwarfism.html

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The MAGIC Foundation: http://www.magicfoundation.org/ Professional Resources

You may also be interested in these resources, which are designed for healthcare professionals and researchers. •

Gene Reviews - Clinical summary: http://www.genetests.org/query?dz=achondroplasia

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Gene Tests - DNA tests ordered by healthcare professionals: http://www.genetests.org/query?testid=2789

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ClinicalTrials.gov - Linking patients to medical research: http://clinicaltrials.gov/search/condition=%22achondroplasia%22?recruiting=false

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PubMed - Recent literature: http://ghr.nlm.nih.gov/condition=achondroplasia/show/PubMed;jsessionid=EE42AE9 5D313DDE2504E562C955E927E

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OMIM - Genetic disorder catalog: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=100800

References These sources were used to develop the Genetics Home Reference condition summary on achondroplasia. •

Gene Review

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Greenberg Center for Skeletal Dysplasias

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Horton WA, Lunstrum GP. Fibroblast growth factor receptor 3 mutations in achondroplasia and related forms of dwarfism. Rev Endocr Metab Disord. 2002 Dec;3(4):381-5. Review. No abstract available. PubMed citation

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Horton WA. Recent milestones in achondroplasia research. Am J Med Genet A. 2006 Jan 15;140(2):166-9. No abstract available. PubMed citation

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Scriver, Charles R; The metabolic & molecular bases of inherited disease; 8th ed.; New York : McGraw-Hill, c2001. p5379-5395. NLM Catalog

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Vajo Z, Francomano CA, Wilkin DJ. The molecular and genetic basis of fibroblast growth factor receptor 3 disorders: the achondroplasia family of skeletal dysplasias, Muenke craniosynostosis, and Crouzon syndrome with acanthosis nigricans. Endocr Rev. 2000 Feb;21(1):23-39. Review. PubMed citation

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A summary of the gene related to achondroplasia is provided below:

What Is the Official Name of the FGFR3 Gene?4 The official name of this gene is “fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism).” FGFR3 is the gene's official symbol. The FGFR3 gene is also known by other names, listed below.

What Is the Normal Function of the FGFR3 Gene? The FGFR3 gene provides instructions for making a protein called fibroblast growth factor receptor 3. This protein is part of a family of fibroblast growth factor receptors that share similar structures and functions. These proteins play a role in several important cellular processes, including regulation of cell growth and division, determination of cell type, formation of blood vessels, wound healing, and embryo development. The FGFR3 protein spans the cell membrane, so that one end of the protein remains inside the cell and the other end projects from the outer surface of the cell. This positioning of the protein allows it to interact with specific growth factors outside the cell and to receive signals that control growth and development. When these growth factors attach to the FGFR3 protein, the protein triggers a cascade of chemical reactions inside the cell that instructs the cell to undergo certain changes, such as maturing to take on specialized functions. The FGFR3 protein is involved in the development and maintenance of bone and brain tissue. Researchers believe that this receptor regulates bone growth by limiting the formation of bone from cartilage (a process called ossification), particularly in the long bones.

Adapted from the Genetics Home Reference of the National Library of Medicine: http://ghr.nlm.nih.gov/gene=fgfr3;jsessionid=EE42AE95D313DDE2504E562C955E927E.

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What Conditions Are Related to the FGFR3 Gene? Achondroplasia - Caused by Mutations in the FGFR3 Gene Two mutations in the FGFR3 gene cause more than 99 percent of cases of achondroplasia. Both mutations lead to the same change in building blocks (amino acids) that make up the fibroblast growth factor receptor 3 protein. Specifically, the amino acid glycine is replaced with the amino acid arginine at protein position 380 (written as Gly380Arg or G380R). Researchers believe that this genetic change causes the receptor to be overly active, which leads to the disturbances in bone growth seen with this disorder. Crouzonodermoskeletal Syndrome - Caused by Mutations in the FGFR3 Gene Two mutations in the FGFR3 gene cause more than 99 percent of cases of achondroplasia. Both mutations lead to the same change in building blocks (amino acids) that make up the fibroblast growth factor receptor 3 protein. Specifically, the amino acid glycine is replaced with the amino acid arginine at protein position 380 (written as Gly380Arg or G380R). Researchers believe that this genetic change causes the receptor to be overly active, which leads to the disturbances in bone growth seen with this disorder. Hypochondroplasia - Caused by Mutations in the FGFR3 Gene A single FGFR3 mutation has been identified in people with Crouzonodermoskeletal syndrome. This genetic change replaces the amino acid alanine with the amino acid glutamic acid at position 391 of the fibroblast growth factor receptor 3 protein (written as Ala391Glu or A391E). Researchers have not determined how this mutation leads to the signs and symptoms of this disorder, but the altered receptor appears to disrupt the normal growth of skull bones and affect skin pigmentation. Muenke Syndrome - Caused by Mutations in the FGFR3 Gene Several mutations in the FGFR3 gene have been identified in people with hypochondroplasia. Many cases are caused by one of two specific FGFR3 mutations, both of which lead to the same change in amino acids in the fibroblast growth factor receptor 3 protein. Specifically, the amino acid asparagine is replaced with the amino acid lysine at protein position 540 (written as Asn540Lys or N540K). Other FGFR3 mutations probably cause a small number of cases of hypochondroplasia. Although the effects of these mutations have not been explained, they probably cause the receptor to be mildly overactivated, which leads to the disturbances in bone growth seen with this disorder. SADDAN - Caused by Mutations in the FGFR3 Gene A single mutation in the FGFR3 gene has been shown to cause Muenke syndrome. This change substitutes the amino acid arginine for the amino acid proline at position 250 in the fibroblast growth factor receptor 3 protein (written as Pro250Arg or P250R). This mutation

Studies

results in the production of a receptor that is overly active, which allows the bones of the skull to fuse before they should. Thanatophoric Dysplasia - Caused by Mutations in the FGFR3 Gene One mutation in the FGFR3 gene has been identified in people with SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans). This genetic change substitutes the amino acid methionine for the amino acid lysine at position 650 of the fibroblast growth factor receptor 3 protein (written as Lys650Met or K650M). Researchers believe that this mutation strongly overactivates the FGFR3 protein, which leads to severe problems with bone growth. It remains uncertain how the mutation disrupts brain development or causes acanthosis nigricans (a skin disorder characterized by thick, dark, velvety skin). Bladder Cancer - Associated with the FGFR3 Gene At least 10 mutations in the FGFR3 gene have been identified in people with thanatophoric dysplasia type I. Most of these mutations change a single amino acid in the fibroblast growth factor receptor 3 protein. The most common mutation substitutes the amino acid cysteine for the amino acid arginine at protein position 248 (written as Arg248Cys or R248C). Other mutations cause the protein to be longer than normal. Other Disorders - Caused by Mutations in the FGFR3 Gene Some gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes, which are called somatic mutations, are not inherited. Somatic mutations in the FGFR3 gene are associated with some cases of bladder cancer. These mutations overactivate the fibroblast growth factor receptor 3 protein, which likely directs bladder cells to grow and divide in the absence of signals from outside the cell. This uncontrolled cell division leads to the formation of a bladder tumor. Other Cancers - Associated with the FGFR3 Gene Mutations in the FGFR3 gene also cause platyspondylic lethal skeletal dysplasia, San Diego type. This skeletal disorder is characterized by severe problems with bone growth similar to thanatophoric dysplasia. Most mutations that cause this disorder change single amino acids in the FGFR3 protein. The altered protein is improperly folded and cannot be transported to the cell membrane. Instead, it accumulates within cartilage cells (chondrocytes) and forms clumps called inclusion bodies. The absence of normal FGFR3 signaling and the formation of inclusion bodies probably disrupt the normal development of bones, leading to the skeletal abnormalities characteristic of platyspondylic lethal skeletal dysplasia, San Diego type.

Where Is the FGFR3 Gene Located? Cytogenetic Location: 4p16.3

Achondroplasia

Molecular Location on chromosome 4: base pairs 1,765,420 to 1,780,395

The FGFR3 gene is located on the short (p) arm of chromosome 4 at position 16.3. More precisely, the FGFR3 gene is located from base pair 1,765,420 to base pair 1,780,395 on chromosome 4.

References These sources were used to develop the Genetics Home Reference gene summary on the FGFR3 gene. •

Brodie SG, Kitoh H, Lachman RS, Nolasco LM, Mekikian PB, Wilcox WR. Platyspondylic lethal skeletal dysplasia, San Diego type, is caused by FGFR3 mutations. Am J Med Genet. 1999 Jun 11;84(5):476-80. PubMed citation

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Cappellen D, De Oliveira C, Ricol D, de Medina S, Bourdin J, Sastre-Garau X, Chopin D, Thiery JP, Radvanyi F. Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas. Nat Genet. 1999 Sep;23(1):18-20. No abstract available. PubMed citation

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Chen L, Deng CX. Roles of FGF signaling in skeletal development and human genetic diseases. Front Biosci. 2005 May 1;10:1961-76. PubMed citation

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Cohen MM Jr. Some chondrodysplasias with short limbs: molecular perspectives. Am J Med Genet. 2002 Oct 15;112(3):304-13. Review. PubMed citation

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Coumoul X, Deng CX. Roles of FGF receptors in mammalian development and congenital diseases. Birth Defects Res C Embryo Today. 2003 Nov;69(4):286-304. Review. PubMed citation

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Eswarakumar VP, Lax I, Schlessinger J. Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev. 2005 Apr;16(2):139-49. Epub 2005 Feb 1. PubMed citation

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Kimura T, Suzuki H, Ohashi T, Asano K, Kiyota H, Eto Y. The incidence of thanatophoric dysplasia mutations in FGFR3 gene is higher in low-grade or superficial

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bladder carcinomas. Cancer. 2001 Nov 15;92(10):2555-61. Erratum in: Cancer 2002 Apr 1;94(7):2117. PubMed citation •

L'Hote CG, Knowles MA. Cell responses to FGFR3 signalling: growth, differentiation and apoptosis. Exp Cell Res. 2005 Apr 1;304(2):417-31. Epub 2004 Dec 16. Review. PubMed citation

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Lievens PM, Liboi E. The thanatophoric dysplasia type II mutation hampers complete maturation of fibroblast growth factor receptor 3 (FGFR3), which activates signal transducer and activator of transcription 1 (STAT1) from the endoplasmic reticulum. J Biol Chem. 2003 May 9;278(19):17344-9. Epub 2003 Mar 06. PubMed citation

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van Rhijn BW, van Tilborg AA, Lurkin I, Bonaventure J, de Vries A, Thiery JP, van der Kwast TH, Zwarthoff EC, Radvanyi F. Novel fibroblast growth factor receptor 3 (FGFR3) mutations in bladder cancer previously identified in non-lethal skeletal disorders. Eur J Hum Genet. 2002 Dec;10(12):819-24. PubMed citation

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Wilkie AO. Bad bones, absent smell, selfish testes: the pleiotropic consequences of human FGF receptor mutations. Cytokine Growth Factor Rev. 2005 Apr;16(2):187-203. Epub 2005 Apr 1. PubMed citation

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Zieger K, Dyrskjot L, Wiuf C, Jensen JL, Andersen CL, Jensen KM, Orntoft TF. Role of activating fibroblast growth factor receptor 3 mutations in the development of bladder tumors. Clin Cancer Res. 2005 Nov 1;11(21):7709-19. PubMed citation

Federally Funded Research on Achondroplasia The U.S. Government supports a variety of research studies relating to achondroplasia. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.5 CRISP (Computerized Retrieval of Information on Scientific Projects) CRISP is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to achondroplasia. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore achondroplasia. The following is typical of the type of information found when searching the CRISP database for achondroplasia: 5

Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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Achondroplasia

Project Title: DEVELOPMENTAL ACTIVITIES OF LATENT TGF-B BINDING PROTEIN Principal Investigator & Institution: Rifkin, Daniel B.; Professor; Cell Biology; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2004; Project Start 01-DEC-1983; Project End 30-JUN-2006 Summary: The latent TGF-beta binding proteins (LTBP) comprise a family of four structurally related proteins that were originally described as part of the latent TGF-beta complex consisting of the TGF-beta dimer, the TGF-beta propeptides noncovalently bound to TGF-beta, and LTBP is thought to help control the activation of latent TGFbeta and to ensure that TGF-beta is released at the correct place and time. In order to gain insight into the functional role(s) of the LTBPs, we have created an LTBP-3 null mouse. This mouse has skeletal and cranial abnormalities that are similar to those observed in achondroplasia and Cruzon syndrome. To characterize potential roles for LTBPs in early development we have examined the distribution and function of LTBP-1 and -3 in Xenopus embryos. The distribution of LTBP-3 is restricted primarily to the cranial region. LTBP-1 has a widespread distribution, and in the early embryo its distribution is similar to that of proteins expressed by Spemann's organizer and that are responsible for dorsal patterning in the developing embryo. We have observed that expression of a truncated form of LTBP-1 in ventral cells of early embryos results in secondary dorsal axis formation in the ventral region. In this application, we propose three aims designed to clarify the role of LTBPs in development. In Aim 1 we will explore the molecular mechanism for the skeletal abnormalities in LTBP-3-/- mice. We will test the hypothesis that the phenotype results from excess formation of active TGFbeta in the absence of the normal binding protein by utilizing in vitro and in vivo approaches coupled with mouse molecular genetics. In Aim 2 we will address possible redundancy and/or functional ovelap within the LTBP family by generating an LTBP-4/- mouse. This animal will be studied together with LTBP-3 and LTBP-1 null animals to discern the relative contributions of specific family members to mouse physiology. In Aim 3 we will characterize the role of LTBP-1 in Xenopus embryo patterning. We will characterize the mechanism of dorsalization, the ligand bound, the mechanism of binding, and how this contributes to early patterning. In sum, the experiments outlined will yield information on the fundamental biology of LTBP. This information may have relevance in understanding developmental events in connective tissues. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FGF RECEPTOR SIGNALING IN BONE DEVELOPMENT Principal Investigator & Institution: Schlessinger, Joseph; Pharmacology; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2005; Project Start 17-DEC-2004; Project End 30-NOV-2009 Summary: (provided by applicant): Fibroblast growth factors (FGFs) and their surface receptors (FGFRs) are critical components of many important biological processes including bone development. The four known FGFRs (FGFR1-FGFR4) are receptor tyrosine kinases (RTKs) activated by binding FGFs and heparin or heparan sulfate proteoglycans to their extracellular ligand binding domain resulting in FGFR dimerization and protein tyrosine kinase activation. It has been shown that the docking protein FRS2 plays a major role in mediating the intracellular signaling pathways following FGF stimulation. Other proteins implicated in FGF signaling include Shc, Gab1, Shp2 and Stat1 among others. Gene inactivation experiments in mice have shown that FGFR2 and FGFR3 play an important role in bone development. Moreover,

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mutations primarily in Fgfr2 and Fgfr3 were shown to be responsible for a variety of bone and skeletal disorders including Crouzon, Apert, Jackson- Weiss, achondroplasia and thanatophoric dysplasia syndromes. The goal of this proposal is to obtain a comprehensive view of the intracellular signaling pathways that are responsible for mediating bone development in response to FGFR2 and FGFR3 activation. The specific aims of this proposal are to: (1) investigate the specific roles of the Fgfr3b and Fgfr3c isoforms in bone development by creating isoform specific knock-out mice, (2) develop genetically modified mice to explore the biological role of the docking protein FRS2 in Fgfr2c mediated bone development, (3) determine the role of FRS2 in human Icraniosynostosis syndrome using murine models, (4) identify FRS2 dependent and independent signaling Ipathways downstream of FGFR2 and FGFR3, and (5) determine the role of the SH2 domain containing IProtein 3BP2 in signaling via FGFR2 and FGFR3. Mutations in 3BP2 were found in cherubism, an lautosomal dominant inherited syndrome characterized by excessive bone degradation. Our goals will be accomplished by applying genetic, biochemical, structural and cell biological approaches. The information obtained from these studies will provide a detailed molecular view of how FGF signaling mediated by FGFR2 and FGFR3 and the docking protein FRS2 control bone development. It will also provide a framework for understanding diseases caused by mutations in FGFRs enabling the design of novel treatments for skeletal disorders such as craniosynostosis, achondroplasia, hypochondroplasia and thanatophoric dysplasia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC ANALYSIS USING SPERM TYPING Principal Investigator & Institution: Arnheim, Norman; Professor; Biological Sciences; University of Southern California Department of Contracts and Grants Los Angeles, Ca 90033 Timing: Fiscal Year 2006; Project Start 01-SEP-1985; Project End 31-AUG-2010 Summary: (provided by applicant): Project Summary: In humans, there is a sizable burden of inherited mutations that contributes to ill health throughout the world. This includes vast numbers of people with common hemoglobinopathies caused by a single gene alteration (sickle cell anemia, alpha- and beta-thalassemia) and genetic variants that contribute to the burden of "common" diseases present in all populations such as cardiovascular disease, cancer, and diabetes. The bulk of this morbidity and mortality arises from transmission of mutant genes from affected or carrier parents to their children. Some affected individuals also arise each generation as a result of inheriting a de novo germline mutation from unaffected parents. Although this is relatively rare, new germline mutations are the sole source of the heritable genetic variation that contributes not only to the "genetic load" of our species but also to the raw materials for adaptive evolution. Our proposal is focused on studying new mutations that occur in the human male germline using a new set of molecular tools to analyze sperm DNA. We plan to study two dominantly inherited conditions, achondroplasia, and Apert syndrome. Our goal is to help explain why the chance of a father having an affected child with a new mutation increases with his age and whether fathers of sporadic cases have the same susceptibility to mutation as men in the general population. In addition, we will test the hypothesis that germline stem cells heterozygous for one of these mutations may have a selective advantage over wild type cells thereby explaining the unexpectedly high mutation frequency typical of both conditions. Relevance: The illness and death due to human genetic disease results from the transmission of mutant genes from affected or carrier parents to their children and the inheritance each generation of

Achondroplasia

new mutations. Our proposal is focused on studying the frequency of new mutations that occur in human sperm using a new set of molecular tools. We plan to study achondroplasia and Apert syndrome with the goal of understanding why the chance of a father transmitting a new mutation to his child increases with his age. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR BIOLOGY OF OSTEOARTHRITIS Principal Investigator & Institution: Jimenez, Sergio A.; Professor; Medicine; Thomas Jefferson University 201 South 11Th Street Philadelphia, Pa 191075587 Timing: Fiscal Year 2004; Project Start 01-DEC-1988; Project End 31-MAR-2007 Summary: The overall aim of this Program Project is to provide a mechanistic understanding of how different mutations in the genes encoding several cartilage specific macromolecules such as type II procollagen, type IX procollagen and cartilage oligomeric matrix protein (COMP) result in the clinical phenotypes of chondrodysplasia and premature osteoarthritis, and to gain a detailed understanding of the effects of these mutations on the structure and biochemistry of cartilage matrix and on the process of chondrogenic differentiation. In addition, the Program Project will examine the role of novel genes expressed in cartilage which were identified employing differential gene expression profiling on the functions of articular cartilage. The work proposed is a logical extension of the research completed during the previous years of funding. Project 1 will extend the previous identification of COMP mutations in patients with multiple ephyseal dysplasia and pseudo achondroplasia to examine the mechanisms by which these mutations alter chondrogenesis and cartilage differentiation. The proposed studies will employ gene replacement (knock-in) technology in mice and retroviral gene transfer in vitro to determine the mechanisms whereby the mutations cause the clinical phenotype. Project 2 will examine the mechanisms by which different mutations in COL2AI and in COL9A2 result in specific phenotypes and will determine the effects of the mutations on collagen supramolecular assembly and structure by analyzing in vitro fibril formation employing electron microscopy and atomic force microscopy. The find Project will take advantage of previous gene expression profiling results which identified several novel genes expressed in human chondrocytes to unravel their function within cartilage. We expect that the results of this multi-faceted approach will provide a greater understanding of the role that mutations in genes encoding extracellular matrix cartilage proteins play on the pathogenesis of hereditary osteoarthritis and other related diseases. We also expect that the results will have broader implications towards the understanding of the pathogenic mechanisms of nonheritable forms of OA and will also provide novel information regarding the biology of chondrogenesis and chondrocyte function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PEX7 AND IT'S ROLE IN THE PATHOGENESIS OF RCDP Principal Investigator & Institution: Braverman, Nancy; Pediatrics; Johns Hopkins University W400 Wyman Park Building Baltimore, Md 212182680 Timing: Fiscal Year 2004; Project Start 28-FEB-2001; Project End 31-JAN-2006 Summary: (Adapted from investigator's abstract): Rhizomelic chondrodysplasio punctata (RCDP) is a peroxisome biogenesis disorder characterized by cataracts, skeletal abnormalities, profound growth failure and mental retardation. RCDP is inherited as an autosomal recessive trait and is caused by mutations in PEX7, which encodes Pex7p, the receptor for peroxisomal enzymes having a PTS2 sequence. The specific steps involved

Studies

in the import of PTS2 proteins into peroxisomes are not known, but the P.I. favors a model in which Pex7p binds PTS2 proteins in the cytosol and transports them to the peroxisome. Pex7p contains six WD40 motifs that determine a beta propeller, a structure that provides multiple rigid surfaces for protein interactions. In RCDP, defective function of PTS2 enzymes is thought to produce unknown metabolic alterations that determine the RCDP phenotype. The overall goal of this proposal is to study the molecular and cellular biology of Pex7p and the pathogenesis of RCDP. The P.I. will achieve this by identification and functional analysis of disease related PEX7 mutations in 50+ RCDP probands, and functional analysis of wild type Pex7p. Dr. Braverman will evaluate Pex7p expression, subcellular location and ability to mediate PTS2 protein import. She will also determine the regions of Pex7p that bind PTS2 and interact with other peroxins. These studies will define the steps in PTS2 protein import and allow correlation of PEX7 defects with variations in RCDP phenotypes. The P.I. will generate a murine model of RCDP to investigate the biochemical alterations in PTS2 protein pathways and their relation to tissue pathology. The proposed strategy will utilize cre/lox technologies to engineer hypomorphic, null and conditional PEX7 alleles and produce mice with combinations of these alleles to develop useful models of RCDP. These mice will be characterized by clinical, radiological, histological and biochemical evaluations. This information will contribute to understanding the pathophysiology of RCDP as well as the normal biology of peroxisome assembly and function in bone, lens and CNS development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF FGF SIGNALING IN BONE DEVELOPMENT Principal Investigator & Institution: Basilico, Claudio; Professor and Chairman; Microbiology; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2004; Project Start 01-FEB-2001; Project End 31-DEC-2005 Summary: Skeletal morphogenesis is controlled by a network of signaling molecules that first determine the fate of undifferentiated stem cells of the mesenchymal lineage and then regulate the proliferation and differentiation of committed osteogenic cells. Among the signaling molecules which influence bone morphogenesis, fibroblast growth factors (FGF) and their cognate receptors (FGFR) have been recently shown to play a major role both in endochondral and intramembranous bone formation. Activating mutations in FGFR3 have been shown to be responsible for several genetic forms of human dwarfism, and other activating mutations in FGFR1, FGFR2 and FGFR3 have been linked to many craniosynostosis syndromes. Mouse genetic experiments have confirmed that unregulated FGF signaling causes bone malformations and suggested that FGFs may act as negative regulators of bone growth. However, the molecular mechanisms through which FGFs influence the proliferation of differentiation of osteogenic cells (e.g. chondrocytes and osteoblasts) remain to be elucidated. The goal of this research project is to study the response to FGF signaling of chondrocytes. We have shown that FGF treatment inhibits the proliferation of chondrocytes, and that this inhibition requires activation of the STAT-1 pathway. Using organ cultures of metatarsal bones rudiments of E15 murine embryos we have also shown that FGFs regulate chondrocyte proliferation and bone development and that this effect also requires STAT1. We wish to understand the molecular mechanisms underlying the growth inhibitory response of chondrocytes to FGF signaling and how FGF signaling affects chondrocyte proliferation and differentiation. We will study 1) the signal transduction pathways activated by FGF receptors in chondrocytes with an emphasis on the mechanisms

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leading to activation on STAT-1, which plays an essential role in the chondrocyte response to FGF; 2) how the progress of the differentiation program which takes place during organ culture of bone rudiments from murine embryos is affected by FGF treatment or by molecules in the FGF signaling pathways; 3) the effect of modulating FGF signaling on bone morphogenesis in vivo, using transgenic and knockout mice, to verify how STAT-1 influences long bone development and chondrodysplasia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE DEVELOPMENT

THE

MAPK

PATHWAY

CRANIAL

BASE

Principal Investigator & Institution: Murakami, Shunichi; Orthopaedics; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2006; Project Start 01-MAR-2006; Project End 28-FEB-2008 Summary: (provided by applicant): The proper growth of the cranial base is essential for normal craniofacial development. Similar to long bones in the limbs, the cranial base is formed through endochondral ossification. The cranial base grows at the synchondrosis, a growth-plate-like cartilage that connects bones. Activating mutations in FGFR3 cause the most common forms of human dwarfisms, achondroplasia and thanatophoric dysplasias. The increased activity of FGFR3 causes hypoplasia of the cranial base, which results in malocclusion requiring orthodontic procedures and narrow foramen magnum that could cause sudden death of infants. Intracellular signaling pathways that mediate the actions of FGFR3 are of keen interest. Our recent genetic experiments have strongly suggested that the ERK1/ERK2 MARK pathway in chondrocytes controls growth and closure of the cranial base synchondroses. We hypothesize that ERK1 and ERK2 in chondrocytes coordinate chondrocyte differentiation and bone formation in the cranial base and long bones. We will examine the precise roles of ERK1 and ERK2 in chondrocytes by pursuing the following Specific Aims: 1) We will inactivate ERK2 in chondrocytes using the Cre-loxP system. We will further inactivate ERK2 in chondrocytes of ERK1-null mice to totally inactivate MARK in chondrocytes. These experiments will greatly advance our knowledge about the roles of ERK1 and ERK2 in endochondral ossification. The elucidation of the mechanisms of endochondral bone growth will eventually lead to the development of new therapies to control bone growth in the cranial base and long bones in various skeletal disorders. Relevance to public health: This study aims to identify the roles of ERK1 and ERK2 in the bone growth using genetically engineered mouse models. This study will provide insights that could be used to control growth of bones that are formed from cartilage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SEEKING THE PHYSICAL BASIS OF ACHONDROPLASIA Principal Investigator & Institution: Hristova, Kalina; Professor; Materials Science and Engr; Johns Hopkins University W400 Wyman Park Building Baltimore, Md 212182680 Timing: Fiscal Year 2004; Project Start 01-MAY-2004; Project End 30-APR-2009 Summary: (provided by applicant): Receptor tyrosine kinases (RTKs) conduct biochemical signals via lateral dimerization in the plasma membrane. The transmembrane (TM) domains of RTKs play an important role in the dimerization process. A single amino acid mutation in RTK TM domains can cause a defect in cell signaling and result in pathological phenotype. For instance, achondroplasia, the most common form of human dwarfism, is linked to a single amino acid mutation (Gly380-toArg) in the TM segment of one RTK, fibroblast growth factor receptor 3 (FGFR3) in more

Studies

than 97% of all studied cases. Nine years after the discovery of the genetic cause of dwarfism, we have put forward a testable hypothesis for the structural determinants of achondroplasia. We seek to test this hypothesis, and elucidate the structural and thermodynamic consequences of the achondroplasia mutation. We propose to: (1) Determine the dimerization propensities for wild-type and mutant TM domains (TMwt and TMmut) in model systems using Fluorescence Resonance Energy Transfer (FRET), (2) Determine the structures of wild-type and mutant TM dimers using site-directed mutagenesis, FRET, NMR, and molecular modeling, (3) Determine whether Arg380 resides inside the hydrocarbon core of the bilayer, or in its interfacial region, and (4) Assess the ability of mutant TM domain to inhibit unregulated FGFR3 signaling in fibroblasts. The proposed work will (1) enhance our knowledge of the mechanism of dimerization of RTKs, and of cell-signaling across the plasma membrane in general, (2) shed light on the molecular basis of achondroplasia, and (3) pave the way for new treatment options for achondroplasia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SKELETAL DYSPLASIAS--INTERNATIONAL REGISTRY Principal Investigator & Institution: Rimoin, David L.; Professor and Chairman; La Biomed Res Inst/ Harbor Ucla Med Ctr 1124 W Carson St, Bldg N-14 Torrance, Ca 905022052 Timing: Fiscal Year 2004 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TARGETED MOUSE MODELS FOR STUDYING SKELETAL DYSPLASIA Principal Investigator & Institution: Briggs, Michael D.; Senior Research Fellow; University of Manchester Research Office, Christie Bldg Manchester, Timing: Fiscal Year 2004; Project Start 27-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): As a group of heterogeneous diseases the osteochondrodysplasias have a complex aetiology, but are likely to share similar bask mechanisms of disease initiation, progression and end-stage pathology. In this context the principle objective of the proposed work is to determine the molecular, cell and extracellular matrix pathology of three distinct chondrodysplasia phenotypes, which result from mutations in the C-terminal globular domains of two different structural proteins that are important for normal bone development. From this approach we can expect to identify common basic mechanisms and learn general principles about genotype-phenotype correlations in other chondrodysplasia phenotypes. These data will ultimately help in developing therapeutic strategies that might be targeted to a range of individual phenotypes. Specifically, we will generate knock-in mouse models of (i) pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) resulting from mutations in the C-terminal globular domain of cartilage oligomeric matrix protein (COMP), and (ii) metaphyseal chondrodysplasia type Schmid (MCDS) resulting from a mutation in the C-terminal globular domain of type X Collagen. We will use these targeted mouse models to determine in vivo the disease pathology by using immunohistochemistry, transmission electron microscopy, in situ hybridisation and proteornics to study in-depth the affected tissues to understand the pathological sequence of events and secondary mechanisms of pathogenesis. Furthermore, we will use cells and tissues from these mice to develop in vitro approaches for studying the disease processes,

Achondroplasia

thereby fully exploiting the targeted mouse models as we establish, test and compare in vivo/in vitro correlations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with achondroplasia, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type achondroplasia (or synonyms) into the search box, and click Go. The following is the type of output you can expect from PubMed for achondroplasia (hyperlinks lead to article summaries): •

A 4-year-old boy with fever. Achondroplasia. Author(s): Charrow J. Source: Pediatric Annals. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16092625&query_hl=28&itool=pubmed_docsum

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A case of achondroplasia with severe respiratory failure, profound developmental delay and hypercreatine phosphokinasemia. Author(s): Imamura Y, Kondoh T, Kamei T, Tsuru A, Shimasaki Y, Kinosh*ta E, Matsumoto T, Moriuchi H. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11059551&query_hl=28&itool=pubmed_docsum

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A differential diagnosis of achondroplasia. Author(s): Silverman FN. Source: Radiologic Clinics of North America. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=5667498&query_hl=28&itool=pubmed_docsum

PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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A gene for achondroplasia-hypochondroplasia maps to chromosome 4p. Author(s): Le Merrer M, Rousseau F, Legeai-Mallet L, Landais JC, Pelet A, Bonaventure J, Sanak M, Weissenbach J, Stoll C, Munnich A, et al. Source: Nature Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8012398&query_hl=28&itool=pubmed_docsum

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A simple and rapid quantitative method of detection of the common achondroplasia mutation: analysis in mismatch repair deficient cells. Author(s): Grewal RP. Source: Genetika. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16161636&query_hl=28&itool=pubmed_docsum

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Abnormal oral mucosal light reflectance in achondroplasia. Author(s): De Felice C, Parrini S, Tonni G, Verrotti A, Del Vecchio A, Latini G. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16731394&query_hl=28&itool=pubmed_docsum

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Absence of correlation between infantile hypotonia and foramen magnum size in achondroplasia. Author(s): Reynolds KK, Modaff P, Pauli RM. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11343336&query_hl=28&itool=pubmed_docsum

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Acanthosis nigricans in a boy with achondroplasia due to the classical Gly380Arg mutation in FGFR3. Author(s): Van Esch H, Fryns JE. Source: Genet Couns. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15517832&query_hl=28&itool=pubmed_docsum

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Accurate diagnosis of a hom*ozygous G1138A mutation in the fibroblast growth factor receptor 3 gene responsible for achondroplasia. Author(s): Satiroglu-Tufan NL, Tufan AC, Semerci CN, Bagci H. Source: The Tohoku Journal of Experimental Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16434832&query_hl=28&itool=pubmed_docsum

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Achondroplasia and cervicomedullary compression: prospective evaluation and surgical treatment. Author(s): Keiper GL Jr, Koch B, Crone KR. Source: Pediatric Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10592476&query_hl=28&itool=pubmed_docsum

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Achondroplasia and enchondromatosis in a female child. Author(s): Nizankowska-Blaz T, Wisz S, Kozlowski K. Source: Skeletal Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12774176&query_hl=28&itool=pubmed_docsum

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Achondroplasia and leukaemia. Author(s): Fraumeni JF Jr, Manning MD. Source: British Medical Journal. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=5231867&query_hl=28&itool=pubmed_docsum

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Achondroplasia and nail-patella syndrome: the compound phenotype. Author(s): Wright MJ, Ain MC, Clough MV, Bellus GA, Hurko O, McIntosh I. Source: Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10978372&query_hl=28&itool=pubmed_docsum

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Achondroplasia associated with pelvic lipomatosis. Author(s): Ono T, Tanaka H, Moriwake T, Kanzaki S, Seino Y. Source: Lancet. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10459944&query_hl=28&itool=pubmed_docsum

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Achondroplasia in diverse Jewish and Arab populations in Israel: clinical and molecular characterization. Author(s): Falik-Zaccai TC, Shachak E, Abeliovitch D, Lerer I, Shefer R, Carmi R, Ries L, Friedman M, Shohat M, Borochowitz Z. Source: Isr Med Assoc J. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10979354&query_hl=28&itool=pubmed_docsum

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Achondroplasia in Turkey is defined by recurrent G380R mutation of the FGFR3 gene. Author(s): Pehlivan S, Ozkinay F, Okutman O, Cogulu O, Ozcan A, Cankaya T, Ulgenalp A. Source: Turk J Pediatr. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12921294&query_hl=28&itool=pubmed_docsum

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Achondroplasia with the FGFR3 1138g-->a (G380R) mutation in two sibs sharing a 4p haplotype derived from their unaffected father. Author(s): Sobetzko D, Braga S, Rudeberg A, Superti-Furga A. Source: Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11186940&query_hl=28&itool=pubmed_docsum

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Achondroplasia with XXY karyotype. Author(s): Sayli BS, Gul D, Cakirbay H. Source: Clinical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8062443&query_hl=28&itool=pubmed_docsum

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Achondroplasia. Author(s): Vijayalakshmi AM. Source: Indian Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12147902&query_hl=28&itool=pubmed_docsum

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Achondroplasia: 3D-CT evaluation of the cervical spine. Author(s): Tsitouridis I, Melidis D, Iosifidis M, Morichovitou A, Goutsaridou F, Stratilati S, Giataganas G, Papastergiou Ch. Source: Stud Health Technol Inform. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15457746&query_hl=28&itool=pubmed_docsum

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Achondroplasia: clinical radiologic features with comment on genetic implications. Author(s): Langer LO Jr, Baumann PA, Gorlin RJ. Source: Clinical Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=5668010&query_hl=28&itool=pubmed_docsum

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Achondroplasia: pre- and postsurgical considerations for midface advancement. Author(s): Barone CM, Eisig S, Jimenez DF, Argamaso RV, Shprintzen RJ. Source: The Cleft Palate-Craniofacial Journal : Official Publication of the American Cleft Palate-Craniofacial Association. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8130246&query_hl=28&itool=pubmed_docsum

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An uncommon G375C substitution in a newborn with achondroplasia. Author(s): Addor MC, Gudinchet F, Truttmann A, Schorderet DF. Source: Genet Couns. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10893668&query_hl=28&itool=pubmed_docsum

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An unusual presentation of achondroplasia. Case report. Author(s): Tubbs RS, Oakes WJ. Source: Journal of Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16370285&query_hl=28&itool=pubmed_docsum

Achondroplasia

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Anaesthetic management of a patient with achondroplasia. Author(s): Krishnan BS, Eipe N, Korula G. Source: Paediatric Anaesthesia. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12846715&query_hl=28&itool=pubmed_docsum

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Analysis of lower extremity alignment in achondroplasia: interobserver reliability and intraobserver reproducibility. Author(s): Inan M, Jeong C, Chan G, Mackenzie WG, Glutting J. Source: Journal of Pediatric Orthopedics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16439907&query_hl=28&itool=pubmed_docsum

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Analysis of the FGFR3 gene in Japanese patients with achondroplasia and hypochondroplasia. Author(s): Katsumata N, Mikami S, Nagashima-Miyokawa A, Nimura A, Sato N, Horikawa R, Tanae A, Tanaka T. Source: Endocrine Journal. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10890199&query_hl=28&itool=pubmed_docsum

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Another condition--not achondroplasia--masquerading in a recent textbook. Author(s): Oestreich AE. Source: Pediatric Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12269255&query_hl=28&itool=pubmed_docsum

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Antenatal diagnosis of achondroplasia with comment on Deuel's "halo" sign. Author(s): Noonan CD. Source: American Journal of Obstetrics and Gynecology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=5659951&query_hl=28&itool=pubmed_docsum

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Arachnoid cyst resulting in tonsillar herniation and syringomyelia in a patient with achondroplasia. Case report. Author(s): Bauer AM, Mueller DM, Oro JJ. Source: Neurosurg Focus. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16398464&query_hl=28&itool=pubmed_docsum

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Bes, Aesop and Morgante: reflections of achondroplasia. Author(s): Hecht F. Source: Clinical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2190719&query_hl=28&itool=pubmed_docsum

Studies

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Bilateral humeral lengthening in achondroplasia. Author(s): Kashiwagi N, Suzuki S, Seto Y, Futami T. Source: Clin Orthop Relat Res. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11603677&query_hl=28&itool=pubmed_docsum

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Biophysical bases for delayed and aberrant motor development in young children with achondroplasia. Author(s): Fowler ES, Glinski LP, Reiser CA, Horton VK, Pauli RM. Source: Journal of Developmental and Behavioral Pediatrics : Jdbp. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9213228&query_hl=28&itool=pubmed_docsum

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Birth prevalence and mutation rate of achondroplasia in the Italian Multicentre Monitoring System for Birth Defects. Author(s): Camera G, Mastroiacovo P. Source: Basic Life Sci. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3071354&query_hl=28&itool=pubmed_docsum

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Bone dysplasia series. Achondroplasia, hypochondroplasia and thanatophoric dysplasia: review and update. Author(s): Lemyre E, Azouz EM, Teebi AS, Glanc P, Chen MF. Source: Canadian Association of Radiologists Journal = Journal L'association Canadienne Des Radiologistes. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10405653&query_hl=28&itool=pubmed_docsum

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Bone formation in achondroplasia. Author(s): Ponseti IV. Source: Basic Life Sci. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3240240&query_hl=28&itool=pubmed_docsum

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Bone marrow transplantation in a patient with chronic myeloid leukemia and achondroplasia. Author(s): Geromin A, Sperotto A, Fanin R, Damiani D, Michieli M, Baccarani M. Source: Haematologica. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9499671&query_hl=28&itool=pubmed_docsum

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Brain morphometric analysis in achondroplasia. Author(s): DiMario FJ Jr, Ramsby GR, Burleson JA, Greensheilds IR. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7898709&query_hl=28&itool=pubmed_docsum

Achondroplasia

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Brain tumor and achondroplasia: a case report and review of the literature. Author(s): McArdle DQ, Sawaya R, Khodadad G. Source: Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=6472587&query_hl=28&itool=pubmed_docsum

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Breathing abnormalities in sleep in achondroplasia. Author(s): Waters KA, Everett F, Sillence D, fa*gan E, Sullivan CE. Source: Archives of Disease in Childhood. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8215519&query_hl=28&itool=pubmed_docsum

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Case report: renal osteodystrophy in association with spinal stenosis in achondroplasia. Author(s): Ong JS, McKenna MJ, Lorigan JG, Watson A, Freaney R. Source: Ir J Med Sci. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8824015&query_hl=28&itool=pubmed_docsum

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Cervicomedullary compression in achondroplasia. Author(s): Ryken TC, Menezes AH. Source: Journal of Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8207526&query_hl=28&itool=pubmed_docsum

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Cervicomedullary compression in young patients with achondroplasia: value of comprehensive neurologic and respiratory evaluation. Author(s): Reid CS, Pyeritz RE, Kopits SE, Maria BL, Wang H, McPherson RW, Hurko O, Phillips JA 3rd, Rosenbaum AE. Source: The Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3559799&query_hl=28&itool=pubmed_docsum

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Cervicomedullary compression with achondroplasia. Author(s): Wassman ER Jr, Rimoin DL. Source: The Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3397808&query_hl=28&itool=pubmed_docsum

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Cervicomedullary cord compression in young children with achondroplasia: value of comprehensive neurologic and respiratory evaluation. Author(s): Reid CS, Pyeritz RE, Kopits SE, Maria BL, Wang H, McPherson RW, Hurko O, Phillips JA. Source: Basic Life Sci. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3240254&query_hl=28&itool=pubmed_docsum

Studies

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Cervicomedullary decompression for foramen magnum stenosis in achondroplasia. Author(s): Bagley CA, Pindrik JA, Bookland MJ, Camara-Quintana JQ, Carson BS. Source: Journal of Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16572633&query_hl=28&itool=pubmed_docsum

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Cervicomedullary junction compression in infants with achondroplasia: when to perform neurosurgical decompression. Author(s): Rimoin DL. Source: American Journal of Human Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7717392&query_hl=28&itool=pubmed_docsum

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Chest wall deformity and respiratory distress in a 17-year-old patient with achondroplasia: CT and MRI evaluation. Author(s): Herman TE, Siegel MJ, McAlister WH. Source: Pediatric Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=1508600&query_hl=28&itool=pubmed_docsum

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Chimeras of the native form or achondroplasia mutant (G375C) of human fibroblast growth factor receptor 3 induce ligand-dependent differentiation of PC12 cells. Author(s): Thompson LM, Raffioni S, Wasmuth JJ, Bradshaw RA. Source: Molecular and Cellular Biology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9199352&query_hl=28&itool=pubmed_docsum

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Chinese achondroplasia is also defined by recurrent G380R mutations of the fibroblast growth factor receptor-3 gene. Author(s): Niu DM, Hsiao KJ, Wang NH, Chin LS, Chen CH. Source: Human Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8682509&query_hl=28&itool=pubmed_docsum

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Choanal atresia with achondroplasia. Author(s): Oestreich AE. Source: The Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7351612&query_hl=28&itool=pubmed_docsum

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Clinical and molecular characteristics of Thai patients with achondroplasia. Author(s): Shotelersuk V, Ittiwut C, Srivuthana S, Wacharasindhu S, Aroonparkmongkol S, Mutirangura A, Poovorawan Y. Source: Southeast Asian J Trop Med Public Health. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11556601&query_hl=28&itool=pubmed_docsum

Achondroplasia

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Clinical variability in achondroplasia. Author(s): Rimoin DL. Source: Basic Life Sci. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3071355&query_hl=28&itool=pubmed_docsum

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Cognitive skills in achondroplasia. Author(s): Brinkmann G, Schlitt H, Zorowka P, Spranger J. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8267016&query_hl=28&itool=pubmed_docsum

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Common mutations in the gene encoding fibroblast growth factor receptor 3 account for achondroplasia, hypochondroplasia and thanatophoric dysplasia. Author(s): Bonaventure J, Rousseau F, Legeai-Mallet L, Le Merrer M, Munnich A, Maroteaux P. Source: Acta Paediatrica (Oslo, Norway : 1992). Supplement. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9055906&query_hl=28&itool=pubmed_docsum

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Comparison of clinical, radiological and molecular findings in Korean infants and children with achondroplasia and hypochondroplasia. Author(s): Shin YL, Choi JH, Kim GH, Yoo HW. Source: J Pediatr Endocrinol Metab. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16355813&query_hl=28&itool=pubmed_docsum

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Compound heterozygosity for the Achondroplasia-hypochondroplasia FGFR3 mutations: prenatal diagnosis and postnatal outcome. Author(s): Chitayat D, Fernandez B, Gardner A, Moore L, Glance P, Dunn M, Chun K, Sgro M, Ray P, Allingham-Hawkins D. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10360393&query_hl=28&itool=pubmed_docsum

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Cone-rod retinal dystrophy and Duane retraction syndrome in a patient with achondroplasia. Author(s): Guirgis MF, Thornton SS, Tychsen L, Lueder GT. Source: Journal of Aapos : the Official Publication of the American Association for Pediatric Ophthalmology and Strabismus / American Association for Pediatric Ophthalmology and Strabismus. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12506285&query_hl=28&itool=pubmed_docsum

Studies

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Constitutive activation of fibroblast growth factor receptor 3 by the transmembrane domain point mutation found in achondroplasia. Author(s): Webster MK, Donoghue DJ. Source: The Embo Journal. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8599935&query_hl=28&itool=pubmed_docsum

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Correction of anterior open bite in a case of achondroplasia. Author(s): Karpagam S, Rabin K, George M, Santhosh K. Source: Indian J Dent Res. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16761710&query_hl=28&itool=pubmed_docsum

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Correction of lumbosacral hyperlordosis in achondroplasia. Author(s): Park HW, Kim HS, Hahn SB, Yang KH, Choi CH, Park JO, Jung SH. Source: Clin Orthop Relat Res. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12966299&query_hl=28&itool=pubmed_docsum

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Craniocervical decompression for cervicomedullary compression in pediatric patients with achondroplasia. Author(s): Aryanpur J, Hurko O, Francomano C, Wang H, Carson B. Source: Journal of Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2384775&query_hl=28&itool=pubmed_docsum

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Craniocervical stenosis and apnea spells in a 2-month-old baby with achondroplasia. Author(s): Najjar JA, Peitersen SE, Carter LP. Source: Journal of Child Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8576562&query_hl=28&itool=pubmed_docsum

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CT of the temporal bone in achondroplasia. Author(s): Cobb SR, Shohat M, Mehringer CM, Lachman R. Source: Ajnr. American Journal of Neuroradiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3143244&query_hl=28&itool=pubmed_docsum

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Cytochrome a3 deficiency in human achondroplasia. Author(s): Mackler B, Davis KA, Grace R. Source: Biochimica Et Biophysica Acta. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3030420&query_hl=28&itool=pubmed_docsum

Achondroplasia

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Deformation across the zone of callotasis during loading. radiostereometric analysis in a patient with achondroplasia. Author(s): Steen H, Kristiansen LP, Finnanger AM, Karrholm J, Reikeras O. Source: Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11347700&query_hl=28&itool=pubmed_docsum

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Deformities of the elbow in achondroplasia. Author(s): Kitoh H, Kitakoji T, Kurita K, Katoh M, Takamine Y. Source: The Journal of Bone and Joint Surgery. British Volume. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12188484&query_hl=28&itool=pubmed_docsum

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Dental anomalies in association with achondroplasia. Report of two cases. Author(s): Brook AH, Winter GB. Source: British Dental Journal. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=5275972&query_hl=28&itool=pubmed_docsum

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Detection of achondroplasia G380R mutation from PCR amplicons by using inosine modified carbon electrodes based on electrochemical DNA chip technology. Author(s): Kara P, Ozkan D, Erdem A, Kerman K, Pehlivan S, Ozkinay F, Unuvar D, Itirli G, Ozsoz M. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=14500035&query_hl=28&itool=pubmed_docsum

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Development of pseudo-achondroplasia over a 30-year period in an adult patient. Author(s): Nores JM, Maroteaux P, Remy JM. Source: Clinical Rheumatology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2667861&query_hl=28&itool=pubmed_docsum

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Developmental abnormalities of the occipital bone in human chondrodystrophies (achondroplasia and thanatophoric dwarfism). Author(s): Marin-Padilla M, Marin-Padilla TM. Source: Birth Defects Orig Artic Ser. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=303528&query_hl=28&itool=pubmed_docsum

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Disappearance of hemifacial spasm after ventriculoperitoneal shunting in a patient with achondroplasia--case report. Author(s): Yamash*ta S, Matsumoto Y, Tamiya T, Kawanishi M, Ogawa D, Nagao S. Source: Neurol Med Chir (Tokyo). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15722610&query_hl=28&itool=pubmed_docsum

Studies

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Distinct patterns of respiratory difficulty in young children with achondroplasia: a clinical, sleep, and lung function study. Author(s): Tasker RC, Dundas I, Laverty A, Fletcher M, Lane R, Stocks J. Source: Archives of Disease in Childhood. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9797588&query_hl=28&itool=pubmed_docsum

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Do parents and grandparents of patients with achondroplasia have a higher cancer risk? Author(s): Stoll C, Feingold J. Source: Am J Med Genet A. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15372518&query_hl=28&itool=pubmed_docsum

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Dwarfism in Dexter cattle is not caused by the mutations in FGFR3 responsible for achondroplasia in humans. Author(s): Usha AP, Lester DH, Williams JL. Source: Animal Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9124710&query_hl=28&itool=pubmed_docsum

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Dynamic lower extremity alignment in children with achondroplasia. Author(s): Inan M, Thacker M, Church C, Miller F, Mackenzie WG, Conklin D. Source: Journal of Pediatric Orthopedics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16791073&query_hl=28&itool=pubmed_docsum

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Early detection of neurological manifestations in achondroplasia. Author(s): Ruiz-Garcia M, Tovar-Baudin A, Del Castillo-Ruiz V, Rodriguez HP, Collado MA, Mora TM, Rueda-Franco F, Gonzalez-Astiazaran A. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9202856&query_hl=28&itool=pubmed_docsum

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Effect of growth hormone therapy in children with achondroplasia: growth pattern, hypothalamic-pituitary function, and genotype. Author(s): Tanaka H, Kubo T, Yamate T, Ono T, Kanzaki S, Seino Y. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9539301&query_hl=28&itool=pubmed_docsum

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Effect of paternal age in achondroplasia, thanatophoric dysplasia, and osteogenesis imperfecta. Author(s): Orioli IM, Castilla EE, Scarano G, Mastroiacovo P. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8588588&query_hl=28&itool=pubmed_docsum

Achondroplasia

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Effects and serum levels of thrombopoietin in a case of chronic thrombocytopenia with achondroplasia. Author(s): Ishiguro A, Nakahata T, Muraoka K, Tahara T, Miyazaki H, Kato T, Inaba Y, Shimbo T. Source: International Journal of Hematology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9220665&query_hl=28&itool=pubmed_docsum

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Effects of lower-leg lengthening on bone mineral density and soft tissue composition of legs in a patient with achondroplasia. Author(s): Takata S, Ikata T, Yonezu H, Inoue A. Source: Journal of Bone and Mineral Metabolism. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11052467&query_hl=28&itool=pubmed_docsum

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Elbow and other upper limb deformities in achondroplasia. Author(s): Bailey JA 2nd. Source: Clin Orthop Relat Res. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=5133334&query_hl=28&itool=pubmed_docsum

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Errors in the diagnosis of achondroplasia. Author(s): Silverman FN, Brunner S. Source: Acta Radiol Diagn (Stockh). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=5298661&query_hl=28&itool=pubmed_docsum

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Errors in the prenatal diagnosis of children with achondroplasia. Author(s): Modaff P, Horton VK, Pauli RM. Source: Prenatal Diagnosis. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8809893&query_hl=28&itool=pubmed_docsum

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Evidence against the structural gene encoding type II collagen (COL2A1) as the mutant locus in achondroplasia. Author(s): Ogilvie D, Wordsworth P, Thompson E, Sykes B. Source: Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3005580&query_hl=28&itool=pubmed_docsum

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Extended laminectomy for spinal stenosis in achondroplasia. Author(s): Streeten E, Uematsu S, Hurko O, Kopits S, Murphy E, Pyeritz R. Source: Basic Life Sci. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3240261&query_hl=28&itool=pubmed_docsum

Studies

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Extradural anaesthesia for caesarean section in achondroplasia. Author(s): Wardall GJ, Frame WT. Source: British Journal of Anaesthesia. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2328185&query_hl=28&itool=pubmed_docsum

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Facial palsy and achondroplasia: a rare association. Author(s): Cerqueiro-Mosquera J, Penrose-Stevens A, Fatah MF. Source: Annals of Plastic Surgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11506333&query_hl=28&itool=pubmed_docsum

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Failed regional anesthesia with reduced spinal bupivacaine dosage in a parturient with achondroplasia presenting for urgent cesarean section. Author(s): DeRenzo JS, Vallejo MC, Ramanathan S. Source: Int J Obstet Anesth. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15795154&query_hl=28&itool=pubmed_docsum

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Failure to early prenatal diagnosis in classic achondroplasia. Author(s): Hall JG, Golbus MS, Graham CB, Pagon RA, Luthy DA, Filly RA. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=474637&query_hl=28&itool=pubmed_docsum

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Familial recurrence of achondroplasia. Author(s): Fitzsimmons JS. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=4061493&query_hl=28&itool=pubmed_docsum

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FGFR3 gene mutation (Gly380Arg) with achondroplasia and i(21q) Down syndrome: phenotype-genotype correlation. Author(s): Chen H, Mu X, Sonoda T, Kim KC, Dailey K, Martinez J, Tuck-Muller C, Wertelecki W. Source: Southern Medical Journal. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10881785&query_hl=28&itool=pubmed_docsum

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FGFR3 gene mutations in transmembrane domain in Chinese achondroplasia and hypochondroplasia patients. Author(s): Yan-Ling G, Ji-Hong N, Guo-Qiang L, Wei W, De-Fen W. Source: Hormone Research. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9554479&query_hl=28&itool=pubmed_docsum

Achondroplasia

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Fibroblast growth factor receptor 3 (FGFR3) gene G1138A mutation in Chinese patients with achondroplasia. Author(s): Wang TR, Wang WP, Hwu WL, Lee ML. Source: Human Mutation. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8844216&query_hl=28&itool=pubmed_docsum

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Fibroblast growth factor receptor 3 mutations in achondroplasia and related forms of dwarfism. Author(s): Horton WA, Lunstrum GP. Source: Reviews in Endocrine & Metabolic Disorders. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12424440&query_hl=28&itool=pubmed_docsum

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Fibroblast growth factor receptor-3 as a therapeutic target for Achondroplasia--genetic short limbed dwarfism. Author(s): Aviezer D, Golembo M, Yayon A. Source: Current Drug Targets. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12816345&query_hl=28&itool=pubmed_docsum

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First trimester increased nuchal translucency associated with fetal achondroplasia. Author(s): Tonni G, Ventura A, De Felice C. Source: American Journal of Perinatology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15838748&query_hl=28&itool=pubmed_docsum

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First-trimester prenatal diagnosis in couple at risk for hom*ozygous achondroplasia. Author(s): Bellus GA, Escallon CS, Ortiz de Luna R, Shumway JB, Blakemore KJ, McIntosh I, Francomano CA. Source: Lancet. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7968151&query_hl=28&itool=pubmed_docsum

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Foramen magnum decompression for hom*ozygous achondroplasia. Author(s): Hecht JT, Butler IJ, Horton WA. Source: Journal of Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2746357&query_hl=28&itool=pubmed_docsum

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Foramen magnum decompression in an infant with hom*ozygous achondroplasia. Case report. Author(s): Moskowitz N, Carson B, Kopits S, Levitt R, Hart G. Source: Journal of Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2909672&query_hl=28&itool=pubmed_docsum

Studies

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Foramen magnum decompression in infants with hom*ozygous achondroplasia. Author(s): Scott RM. Source: Journal of Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2303889&query_hl=28&itool=pubmed_docsum

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Foramen magnum stenosis and bilateral benign subdural collections in achondroplasia: case report. Author(s): Mancuso P, Nicoletti GF, Passanisi M, Albanese V. Source: Journal of Neurosurgical Sciences. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7562034&query_hl=28&itool=pubmed_docsum

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Foramen magnum stenosis in hom*ozygous achondroplasia. Author(s): Hecht JT, Horton WA, Butler IJ, Goldie WD, Miner ME, Shannon R, Pauli RM. Source: European Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3816858&query_hl=28&itool=pubmed_docsum

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Frequency of the appearance of the dominant mutation of achondroplasia in man. Communication I. Ratio of sporadic and familial cases. Author(s): Lunga IN, Meerson EM, Moin ML. Source: Sov Genet. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=4453852&query_hl=28&itool=pubmed_docsum

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Functional health status of adults with achondroplasia. Author(s): Mahomed NN, Spellmann M, Goldberg MJ. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9637420&query_hl=28&itool=pubmed_docsum

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Fusion of the short arms of two X chromosomes in a patient with phenotype of achondroplasia. Author(s): Pena J, Pombo M, Martinon JM, Ansede A, Noya M. Source: J Genet Hum. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=591927&query_hl=28&itool=pubmed_docsum

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Genetic counselling in unexpected familial recurrence of achondroplasia. Author(s): Dodinval P, Le Marec B. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3688033&query_hl=28&itool=pubmed_docsum

Achondroplasia

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Genetics clinics of The Johns Hopkins Hospital. Surgical intervention in achondroplasia. Cervical and lumbar laminectomy for spinal stenosis in achondroplasia. Author(s): Pyeritz RE, Sack GH Jr, Udvarhelyi GB. Source: Johns Hopkins Med J. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7382243&query_hl=28&itool=pubmed_docsum

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Genetics clinics of The Johns Hopkins Hospital. Surgical intervention in achondroplasia. Correction of bowleg deformity in achondroplasia. Author(s): Kopits SE. Source: Johns Hopkins Med J. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7382244&query_hl=28&itool=pubmed_docsum

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Genotype phenotype correlation in achondroplasia and hypochondroplasia. Author(s): Matsui Y, Yasui N, Kimura T, Tsumaki N, Kawabata H, Ochi T. Source: The Journal of Bone and Joint Surgery. British Volume. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9853502&query_hl=28&itool=pubmed_docsum

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Genu varum in achondroplasia. Author(s): Ain MC, Shirley ED, Pirouzmanesh A, Skolasky RL, Leet AI. Source: Journal of Pediatric Orthopedics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16670552&query_hl=28&itool=pubmed_docsum

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Germinal mosaicism in achondroplasia: a family with 3 affected siblings of normal parents. Author(s): Fryns JP, Kleczkowska A, Verresen H, van den Berghe H. Source: Clinical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=6627718&query_hl=28&itool=pubmed_docsum

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Germline and somatic mosaicism in achondroplasia. Author(s): Henderson S, Sillence D, Loughlin J, Bennetts B, Sykes B. Source: Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11186939&query_hl=28&itool=pubmed_docsum

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Gibbal achondroplasia. Author(s): Beighton P, Bathfield CA. Source: The Journal of Bone and Joint Surgery. British Volume. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7263742&query_hl=28&itool=pubmed_docsum

Studies

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Gly369Cys mutation in mouse FGFR3 causes achondroplasia by affecting both chondrogenesis and osteogenesis. Author(s): Chen L, Adar R, Yang X, Monsonego EO, Li C, Hauschka PV, Yayon A, Deng CX. Source: The Journal of Clinical Investigation. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10587515&query_hl=28&itool=pubmed_docsum

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Graded activation of fibroblast growth factor receptor 3 by mutations causing achondroplasia and thanatophoric dysplasia. Author(s): Naski MC, Wang Q, Xu J, Ornitz DM. Source: Nature Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8640234&query_hl=28&itool=pubmed_docsum

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Growth and growth hormone therapy in children with achondroplasia: a two-year experience. Author(s): Stamoyannou L, Karachaliou F, Neou P, Papataxiarchou K, Pistevos G, Bartsocas CS. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9295079&query_hl=28&itool=pubmed_docsum

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Growth curves in achondroplasia. Author(s): Horton WA, Rotter JI, Kaitila I, Gursky J, Hall JG, Shepard TH, Rimoin DL. Source: Birth Defects Orig Artic Ser. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=890105&query_hl=28&itool=pubmed_docsum

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Growth hormone (GH) treatment in achondroplasia. Author(s): Yamate T, Kanzaki S, Tanaka H, Kubo T, Moriwake T, Inoue M, Seino Y. Source: J Pediatr Endocrinol. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8374688&query_hl=28&itool=pubmed_docsum

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Growth hormone therapy in achondroplasia. Author(s): Seino Y, Yamanaka Y, Shinohara M, Ikegami S, Koike M, Miyazawa M, Inoue M, Moriwake T, Tanaka H. Source: Hormone Research. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10971105&query_hl=28&itool=pubmed_docsum

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Growth hormone therapy in achondroplasia. Author(s): Nishi Y, Kajiyama M, Miyagawa S, Fujiwara M, Hamamoto K. Source: Acta Endocrinol (Copenh). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8317186&query_hl=28&itool=pubmed_docsum

Achondroplasia

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Growth hormone therapy in achondroplasia. Author(s): Horton WA, Hecht JT, Hood OJ, Marshall RN, Moore WV, Hollowell JG. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=1632435&query_hl=28&itool=pubmed_docsum

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Growth hormone treatment in 35 prepubertal children with achondroplasia: a fiveyear dose-response trial. Author(s): Hertel NT, Eklof O, Ivarsson S, Aronson S, Westphal O, Sipila I, Kaitila I, Bland J, Veimo D, Muller J, Mohnike K, Neumeyer L, Ritzen M, Hagenas L. Source: Acta Paediatrica (Oslo, Norway : 1992). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16299871&query_hl=28&itool=pubmed_docsum

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Growth of the foramen magnum in achondroplasia. Author(s): Hecht JT, Horton WA, Reid CS, Pyeritz RE, Chakraborty R. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2773998&query_hl=28&itool=pubmed_docsum

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Growth plate cartilage studies in achondroplasia. Author(s): Horton WA, Hood OJ, Machado MA, Campbell D. Source: Basic Life Sci. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3240287&query_hl=28&itool=pubmed_docsum

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Growth-promoting effect of human growth hormone on patients with achondroplasia. Author(s): Okabe T, Nishikawa K, Miyamori C, Sato T. Source: Acta Paediatr Jpn. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=1785332&query_hl=28&itool=pubmed_docsum

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Head growth in achondroplasia: use of ultrasound studies. Author(s): Hall JG, Horton W, Kelly T, Scott CI. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7137217&query_hl=28&itool=pubmed_docsum

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Health supervision for children with achondroplasia. Author(s): Trotter TL, Hall JG; American Academy of Pediatrics Committee on Genetics. Source: Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16140722&query_hl=28&itool=pubmed_docsum

Studies

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Hearing loss and temporal bone structure in achondroplasia. Author(s): Shohat M, Flaum E, Cobb SR, Lachman R, Rubin C, Ash C, Rimoin DL. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8456822&query_hl=28&itool=pubmed_docsum

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Hirschsprung's disease associated with a variant form of achondroplasia, in sister and brother. Author(s): Roberts PA, Mann TP, Rubin J. Source: Proc R Soc Med. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=5811938&query_hl=28&itool=pubmed_docsum

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Histochemical and ultrastructural study of the growth plate in achondroplasia. Author(s): Ippolito E, Maynard JA, Mickelson MR, Ponseti IV. Source: Basic Life Sci. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3240286&query_hl=28&itool=pubmed_docsum

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Histochemistry and ultrastructure of the growth plate in achondroplasia. Author(s): Maynard JA, Ippolito EG, Ponseti IV, Mickelson MR. Source: The Journal of Bone and Joint Surgery. American Volume. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=6165726&query_hl=28&itool=pubmed_docsum

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Histological and histochemical investigations of achondroplastic mice: a possible model of human achondroplasia. Author(s): Bonucci E, Marco AD, Nicoletti B, Petrinelli P, Pozzi L. Source: Growth. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=976768&query_hl=28&itool=pubmed_docsum

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hom*ozygosity for achondroplasia? Report of a possible case, with congenital heart disease and severe mental deficit. Author(s): Morgan BC, Graham CB, Aase JM. Source: Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=5410232&query_hl=28&itool=pubmed_docsum

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hom*ozygous achondroplasia with survival beyond infancy. Author(s): Pauli RM, Conroy MM, Langer LO Jr, McLone DG, Naidich T, Franciosi R, Ratner IM, Copps SC. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=6660245&query_hl=28&itool=pubmed_docsum

Achondroplasia

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hom*ozygous achondroplasia: morphologic and biochemical study of cartilage. Author(s): Stanescu R, Stanescu V, Maroteaux P. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2260574&query_hl=28&itool=pubmed_docsum

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hom*ozygous achondroplasia: US distinction between hom*ozygous, heterozygous, and unaffected fetuses in the second trimester. Author(s): Patel MD, Filly RA. Source: Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7617874&query_hl=28&itool=pubmed_docsum

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Human achondroplasia: defective mitochondrial oxidative energy metabolism may produce the pathophysiology. Author(s): Mackler B, Shepard TH. Source: Teratology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2560262&query_hl=28&itool=pubmed_docsum

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Human growth hormone treatment in prepubertal children with achondroplasia. Author(s): Weber G, Prinster C, Meneghel M, Russo F, Mora S, Puzzovio M, Del Maschio M, Chiumello G. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8834055&query_hl=28&itool=pubmed_docsum

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Hydrocephalus and achondroplasia. A study of 25 observations. Author(s): Pierre-Kahn A, Hirsch JF, Renier D, Metzger J, Maroteaux P. Source: Childs Brain. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7438842&query_hl=28&itool=pubmed_docsum

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Hydrocephalus and chronically increased intracranial pressure in achondroplasia. Author(s): Erdincler P, Dashti R, Kaynar MY, Canbaz B, Ciplak N, Kuday C. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9272288&query_hl=28&itool=pubmed_docsum

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Hydrocephalus in achondroplasia studied by cisternography. Author(s): James AE Jr, Dorst JP, Mathews ES, McKusick VA. Source: Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=5059311&query_hl=28&itool=pubmed_docsum

Studies

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Hydrocephalus in achondroplasia. Author(s): Wise BL. Source: Journal of Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7277018&query_hl=28&itool=pubmed_docsum

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Hydrocephalus in achondroplasia: a possible mechanism. Author(s): Friedman WA, Mickle JP. Source: Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7422111&query_hl=28&itool=pubmed_docsum

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Hydrocephalus in achondroplasia: the possible role of intracranial venous hypertension. Author(s): Steinbok P, Hall J, Flodmark O. Source: Journal of Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2786928&query_hl=28&itool=pubmed_docsum

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Impossible direct laryngoscopy in achondroplasia. A case report. Author(s): Mather JS. Source: Anaesthesia. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=5956576&query_hl=28&itool=pubmed_docsum

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Improved prenatal detection of a fetal point mutation for achondroplasia by the use of size-fractionated circulatory DNA in maternal plasma--case report. Author(s): Li Y, Holzgreve W, Page-Christiaens GC, Gille JJ, Hahn S. Source: Prenatal Diagnosis. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15565648&query_hl=28&itool=pubmed_docsum

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In utero analysis of heterozygous achondroplasia: variable time of onset as detected by femur length measurements. Author(s): Kurtz AB, Filly RA, Wapner RJ, Golbus MS, Rifkin MR, Callen PW, Pasto ME. Source: Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3517360&query_hl=28&itool=pubmed_docsum

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Increased carbohydrate-deficient transferrin concentration and abnormal protein glycosylation of unknown etiology in a patient with achondroplasia. Author(s): Assmann B, Hackler R, Peters V, Schaefer JR, Hoffmann GF. Source: Clinical Chemistry. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10759489&query_hl=28&itool=pubmed_docsum

Achondroplasia

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Information update on Achondroplasia. Author(s): Hall JG. Source: Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7700776&query_hl=28&itool=pubmed_docsum

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Intracranial hemorrhage in achondroplasia. Author(s): Gendell HM, Barmada MA, Maroon JC, Wisotzkey H. Source: Surgical Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=898007&query_hl=28&itool=pubmed_docsum

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Intrauterine osteogenesis imperfecta with arthrogryposis multiplex and regional achondroplasia. Author(s): Guha DK, Rashmi A, Khanduja PC, Kochlar M. Source: Indian Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=5402443&query_hl=28&itool=pubmed_docsum

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Issues surrounding prenatal genetic testing for achondroplasia. Author(s): Gooding HC, Boehm K, Thompson RE, Hadley D, Francomano CA, Biesecker BB. Source: Prenatal Diagnosis. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12378581&query_hl=28&itool=pubmed_docsum

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Japanese sisters with Pfeiffer syndrome and achondroplasia: a mutation analysis. Author(s): Nagase T, Nagase M, Hirose S, Ohmori K. Source: The Journal of Craniofacial Surgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9780920&query_hl=28&itool=pubmed_docsum

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Jugular bulb dehiscence in achondroplasia. Author(s): Pauli RM, Modaff P. Source: International Journal of Pediatric Otorhinolaryngology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10375043&query_hl=28&itool=pubmed_docsum

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Kyphosis and lumbar stenosis in achondroplasia. Author(s): Nelson MA. Source: Basic Life Sci. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3240265&query_hl=28&itool=pubmed_docsum

Studies

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Kyphosis in achondroplasia: probably preventable. Author(s): Hall JG. Source: The Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3335958&query_hl=28&itool=pubmed_docsum

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Leg lengthening: patient selection and management in achondroplasia. Author(s): Saleh M, Burton M. Source: The Orthopedic Clinics of North America. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=1945337&query_hl=28&itool=pubmed_docsum

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Lengthening of the lower limbs and correction of lumbar hyperlordosis in achondroplasia. Author(s): Vilarrubias JM, Cavaliere P, Ginebreda I. Source: Basic Life Sci. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3240272&query_hl=28&itool=pubmed_docsum

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Lengthening of the lower limbs and correction of lumbar hyperlordosis in achondroplasia. Author(s): Vilarrubias JM, Ginebreda I, Jimeno E. Source: Clin Orthop Relat Res. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2293921&query_hl=28&itool=pubmed_docsum

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Lengthening of the lower limbs in patients with achondroplasia and hypochondroplasia. Author(s): Yasui N, Kawabata H, Kojimoto H, Ohno H, Matsuda S, Araki N, Shimomura Y, Ochi T. Source: Clin Orthop Relat Res. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9372781&query_hl=28&itool=pubmed_docsum

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Lethal skeletal dysplasia owing to double heterozygosity for achondroplasia and spondyloepiphyseal dysplasia congenita. Author(s): Young ID, Ruggins NR, Somers JM, Zuccollo JM, Rutter N. Source: Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=1453438&query_hl=28&itool=pubmed_docsum

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Letter: Failure to diagnose achondroplasia in utero. Author(s): Golbus MS, Hall BD. Source: Lancet. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=4132293&query_hl=28&itool=pubmed_docsum

Achondroplasia

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Letter: Serum somatomedin-C in achondroplasia. Author(s): Horton WA, Rimoin DL, Underwood LE, Van Wyk J. Source: The New England Journal of Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=934255&query_hl=28&itool=pubmed_docsum

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Letter: Tolbutamide and achondroplasia. Author(s): Blizzard RM, McKusick VA. Source: Jama : the Journal of the American Medical Association. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=4406604&query_hl=28&itool=pubmed_docsum

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Levels of creatine kinase activity in cartilage of tubular and nontubular bone in relation to pathogenesis of achondroplasia. Author(s): Nogami H, Oohira A, Ogasawara N. Source: Clin Orthop Relat Res. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3581582&query_hl=28&itool=pubmed_docsum

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Limb lengthening for achondroplasia: early experience. Author(s): Price CT. Source: Journal of Pediatric Orthopedics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2794023&query_hl=28&itool=pubmed_docsum

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Limb lengthening in achondroplasia by Ilizarov's method. Author(s): Cattaneo R, Villa A, Catagni M, Tentori L. Source: International Orthopaedics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3182120&query_hl=28&itool=pubmed_docsum

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Limb lengthening in children with achondroplasia. Differences based on gender. Author(s): Ganel A, Horoszowski H. Source: Clin Orthop Relat Res. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8913161&query_hl=28&itool=pubmed_docsum

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Living with achondroplasia in an average-sized world: an assessment of quality of life. Author(s): Gollust SE, Thompson RE, Gooding HC, Biesecker BB. Source: Am J Med Genet A. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12884421&query_hl=28&itool=pubmed_docsum

Studies

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Living with achondroplasia: attitudes toward population screening and correlation with quality of life. Author(s): Gollust SE, Thompson RE, Gooding HC, Biesecker BB. Source: Prenatal Diagnosis. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=14663838&query_hl=28&itool=pubmed_docsum

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Living with achondroplasia: quality of life evaluation following cervico-medullary decompression. Author(s): Ho NC, Guarnieri M, Brant LJ, Park SS, Sun B, North M, Francomano CA, Carson BS. Source: Am J Med Genet A. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15487008&query_hl=28&itool=pubmed_docsum

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Localization of the achondroplasia gene to the distal 2.5 Mb of human chromosome 4p. Author(s): Francomano CA, Ortiz de Luna RI, Hefferon TW, Bellus GA, Turner CE, Taylor E, Meyers DA, Blanton SH, Murray JC, McIntosh I, et al. Source: Human Molecular Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8081365&query_hl=28&itool=pubmed_docsum

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Long-term neurological sequelae in achondroplasia. Author(s): Hecht JT, Butler IJ, Scott CI Jr. Source: European Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=6510432&query_hl=28&itool=pubmed_docsum

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Lung hypoplasia and severe pulmonary hypertension in an infant with double heterozygosity for spondyloepiphyseal dysplasia congenita and achondroplasia. Author(s): Gunthard J, Fliegel C, Ohnacker H, Rutishauser M, Buhler E. Source: Clinical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7586642&query_hl=28&itool=pubmed_docsum

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Lung volume histograms after computed tomography of the chest with threedimensional imaging as a method to substantiate successful surgical expansion of the rib cage in achondroplasia. Author(s): Lugo N, Becker J, Van Bosse H, Campbell W, Evans B, Sagy M. Source: Journal of Pediatric Surgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9607482&query_hl=28&itool=pubmed_docsum

Achondroplasia

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Magnetic resonance imaging in the assessment of medullary compression in achondroplasia. Author(s): Thomas IT, Frias JL, Williams JL, Friedman WA. Source: Am J Dis Child. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3046333&query_hl=28&itool=pubmed_docsum

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Magnetic resonance venography of achondroplasia: correlation of venous narrowing at the jugular foramen with hydrocephalus. Author(s): Moritani T, Aihara T, Oguma E, Makiyama Y, Nishimoto H, Smoker WR, Sato Y. Source: Clinical Imaging. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16632156&query_hl=28&itool=pubmed_docsum

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Management of disabilities associated with achondroplasia. Author(s): Haga N. Source: Journal of Orthopaedic Science : Official Journal of the Japanese Orthopaedic Association. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=14767713&query_hl=28&itool=pubmed_docsum

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Medical complications of achondroplasia: a multicentre patient review. Author(s): Hunter AG, Bankier A, Rogers JG, Sillence D, Scott CI Jr. Source: Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9733026&query_hl=28&itool=pubmed_docsum

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Megalencephaly in thanatophoric dysplasia and in achondroplasia. Author(s): Knisely AS. Source: The Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2585221&query_hl=28&itool=pubmed_docsum

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Mesomelic and rhizomelic short stature: The phenotype of combined Leri-Weill dyschondrosteosis and achondroplasia or hypochondroplasia. Author(s): Ross JL, Bellus G, Scott CI Jr, Abboudi J, Grigelioniene G, Zinn AR. Source: Am J Med Genet A. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12476453&query_hl=28&itool=pubmed_docsum

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Molecular basis for the treatment of achondroplasia. Author(s): Yamanaka Y, Ueda K, Seino Y, Tanaka H. Source: Hormone Research. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=14671399&query_hl=28&itool=pubmed_docsum

Studies

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Molecular defects in achondroplasia and the effects of growth hormone treatment. Author(s): Seino Y, Moriwake T, Tanaka H, Inoue M, Kanzaki S, Tanaka T, Matsuo N, Niimi H. Source: Acta Paediatrica (Oslo, Norway : 1992). Supplement. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10102070&query_hl=28&itool=pubmed_docsum

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Molecular diagnosis in a pregnancy at risk for both spondyloepiphyseal dysplasia congenita and achondroplasia. Author(s): James PA, Shaw J, du Sart D, Craig E, Bateman JF, Savarirayan R. Source: Prenatal Diagnosis. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=14558035&query_hl=28&itool=pubmed_docsum

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MR imaging of the craniovertebral junction, cranium, and brain in children with achondroplasia. Author(s): Kao SC, Waziri MH, Smith WL, Sato Y, Yuh WT, Franken EA Jr. Source: Ajr. American Journal of Roentgenology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2763957&query_hl=28&itool=pubmed_docsum

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MRI study of the lumbar spine in achondroplasia. A morphometric analysis for the evaluation of stenosis of the canal. Author(s): Jeong ST, Song HR, Keny SM, Telang SS, Suh SW, Hong SJ. Source: The Journal of Bone and Joint Surgery. British Volume. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16943471&query_hl=28&itool=pubmed_docsum

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Multiplier method for prediction of adult height in patients with achondroplasia. Author(s): Paley D, Matz AL, Kurland DB, Lamm BM, Herzenberg JE. Source: Journal of Pediatric Orthopedics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15958911&query_hl=28&itool=pubmed_docsum

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Mutation in the gene encoding the fibroblast growth factor receptor-3 in Korean children with achondroplasia. Author(s): Yang SW, Kitoh H, Yamada Y, Goto H, Ogasawara N. Source: Acta Paediatr Jpn. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9745773&query_hl=28&itool=pubmed_docsum

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Mutations causing achondroplasia and thanatophoric dysplasia alter bFGF-induced calcium signals in human diploid fibroblasts. Author(s): Nguyen HB, Estacion M, Gargus JJ. Source: Human Molecular Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9158142&query_hl=28&itool=pubmed_docsum

Achondroplasia

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Mutations in fibroblast growth-factor receptor 3 in sporadic cases of achondroplasia occur exclusively on the paternally derived chromosome. Author(s): Wilkin DJ, Szabo JK, Cameron R, Henderson S, Bellus GA, Mack ML, Kaitila I, Loughlin J, Munnich A, Sykes B, Bonaventure J, Francomano CA. Source: American Journal of Human Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9718331&query_hl=28&itool=pubmed_docsum

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Mutations in the fibroblast growth factor receptor 3 (FGFR3) cause achondroplasia, hypochondroplasia, and thanatophoric dysplasia: Taiwanese data. Author(s): Tsai FJ, Tsai CH, Chang JG, Wu JY. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10482885&query_hl=28&itool=pubmed_docsum

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Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia. Author(s): Rousseau F, Bonaventure J, Legeai-Mallet L, Pelet A, Rozet JM, Maroteaux P, Le Merrer M, Munnich A. Source: Nature. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8078586&query_hl=28&itool=pubmed_docsum

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Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia. Author(s): Shiang R, Thompson LM, Zhu YZ, Church DM, Fielder TJ, Bocian M, Winokur ST, Wasmuth JJ. Source: Cell. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7913883&query_hl=28&itool=pubmed_docsum

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Mutations of the fibroblast growth factor receptor-3 gene in achondroplasia. Author(s): Rousseau F, Bonaventure J, Legeai-Mallet L, Pelet A, Rozet JM, Maroteaux P, Le Merrer M, Munnich A. Source: Hormone Research. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8742128&query_hl=28&itool=pubmed_docsum

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Mutations of the fibroblast growth factor receptor-3 gene in one familial and six sporadic cases of achondroplasia in Japanese patients. Author(s): Ikegawa S, f*ckushima Y, Isomura M, Takada F, Nakamura Y. Source: Human Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7649548&query_hl=28&itool=pubmed_docsum

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Narrowing of thoraco-lumbar spinal canal in achondroplasia. Author(s): Fortuna A, Ferrante L, Acqui M, Santoro A, Mastronardi L. Source: Journal of Neurosurgical Sciences. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2677264&query_hl=28&itool=pubmed_docsum

Studies

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Neuroanatomic and neuropsychological outcome in school-age children with achondroplasia. Author(s): Thompson NM, Hecht JT, Bohan TP, Kramer LA, Davidson K, Brandt ME, Fletcher JM. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10206234&query_hl=28&itool=pubmed_docsum

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Neuroblastoma in a dwarfed newborn. Possible clue to the chromosomal localization of the gene for achondroplasia? Author(s): Verloes A, Massart B, Jossa V, Langhendries JP, Hainaut H, Paquot JP, Koulischer L. Source: Annales De Genetique. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=1952787&query_hl=28&itool=pubmed_docsum

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Neurologic morbidity associated with achondroplasia. Author(s): Hecht JT, Butler IJ. Source: Journal of Child Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2161033&query_hl=28&itool=pubmed_docsum

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Neurological abnormalities in achondroplasia. Author(s): Critchley E. Source: Developmental Medicine and Child Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=5643337&query_hl=28&itool=pubmed_docsum

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Neurological basis of respiratory complications in achondroplasia. Author(s): Nelson FW, Hecht JT, Horton WA, Butler IJ, Goldie WD, Miner M. Source: Annals of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3415202&query_hl=28&itool=pubmed_docsum

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Neurological complications and myelographic features of achondroplasia. Author(s): Galanski M, Herrmann R, Knoche U. Source: Neuroradiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=752129&query_hl=28&itool=pubmed_docsum

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Neurological considerations in achondroplasia. Author(s): Hurko O, Pyeritz R, Uematsu S. Source: Basic Life Sci. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3240245&query_hl=28&itool=pubmed_docsum

Achondroplasia

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Neurological manifestations of pediatric achondroplasia. Author(s): Yamada H, Nakamura S, Tajima M, Kageyama N. Source: Journal of Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7463120&query_hl=28&itool=pubmed_docsum

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Neurological symptoms in achondroplasia. Author(s): Bergstrom K, Laurent U, Lundberg PO. Source: Acta Neurologica Scandinavica. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=5576220&query_hl=28&itool=pubmed_docsum

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Nonrandom association of a type II procollagen genotype with achondroplasia. Author(s): Eng CE, Pauli RM, Strom CM. Source: Proceedings of the National Academy of Sciences of the United States of America. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2991928&query_hl=28&itool=pubmed_docsum

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Obesity in achondroplasia. Author(s): Hecht JT, Hood OJ, Schwartz RJ, Hennessey JC, Bernhardt BA, Horton WA. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3228140&query_hl=28&itool=pubmed_docsum

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Observations on the cause of bowlegs in achondroplasia. Author(s): Stanley G, McLoughlin S, Beals RK. Source: Journal of Pediatric Orthopedics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11744865&query_hl=28&itool=pubmed_docsum

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Observations suggesting allelism of the achondroplasia and hypochondroplasia genes. Author(s): McKusick VA, Kelly TE, Dorst JP. Source: Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=4697848&query_hl=28&itool=pubmed_docsum

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Obstructive sleep apnea in children with achondroplasia: surgical and anesthetic considerations. Author(s): Sisk EA, Heatley DG, Borowski BJ, Leverson GE, Pauli RM. Source: Otolaryngology and Head and Neck Surgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9949360&query_hl=28&itool=pubmed_docsum

Studies

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Occurrence of thanatophoric dysplasia type I (R248C) and hypochondroplasia (N540K) mutations in two patients with achondroplasia phenotype. Author(s): Camera G, Baldi M, Strisciuglio G, Concolino D, Mastroiacovo P, Baffico M. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11754059&query_hl=28&itool=pubmed_docsum

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Optometric screening in achondroplasia, diastrophic dysplasia, and spondyloepiphyseal dysplasia congenita. Author(s): Griffin JR, Ault JE, Sillence DO, Rimoin DL. Source: Am J Optom Physiol Opt. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=6769335&query_hl=28&itool=pubmed_docsum

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Oral findings in a typical case of achondroplasia. Author(s): Celenk P, Arici S, Celenk C. Source: J Int Med Res. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12870378&query_hl=28&itool=pubmed_docsum

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Orthodontic management of achondroplasia in South Africa. Author(s): Stephen L, Holmes H, Roberts T, Fieggen K, Beighton P. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16201001&query_hl=28&itool=pubmed_docsum

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Orthodontic management of achondroplasia. Author(s): Bellardie HH. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16909171&query_hl=28&itool=pubmed_docsum

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Orthodontic treatment of Class II division 1 malocclusion in a patient with achondroplasia. Author(s): Ohba T, Ohba Y, Tenshin S, Takano-Yamamoto T. Source: Angle Orthod. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9709839&query_hl=28&itool=pubmed_docsum

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Orthopaedic aspects of achondroplasia. Author(s): Bailey JA 2nd. Source: The Journal of Bone and Joint Surgery. American Volume. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=5472902&query_hl=28&itool=pubmed_docsum

Achondroplasia

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Orthopedic aspects of achondroplasia in children. Author(s): Kopits SE. Source: Basic Life Sci. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3240253&query_hl=28&itool=pubmed_docsum

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Osteomyelitis variolosa simulating achondroplasia. Author(s): Mohindra Y, Tuli SM. Source: Indian J Pediatr. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=5783822&query_hl=28&itool=pubmed_docsum

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Otologic impairments in achondroplasia: a nosologic assessment. Author(s): Pinelli V, Masi R, Partipilo P, Pierro V, Tieri L. Source: Basic Life Sci. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3240244&query_hl=28&itool=pubmed_docsum

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Overnight growth hormone secretion in achondroplasia: deconvolution analysis, correlation with sleep state, and changes after treatment of obstructive sleep apnea. Author(s): Waters KA, Kirjavainen T, Jimenez M, Cowell CT, Sillence DO, Sullivan CE. Source: Pediatric Research. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8929879&query_hl=28&itool=pubmed_docsum

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Patient with double heterozygosity for achondroplasia and pseudoachondroplasia, with comments on these conditions and the relationship between pseudoachondroplasia and multiple epiphyseal dysplasia, Fairbank type. Author(s): Langer LO Jr, Schaefer GB, Wadsworth DT. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8267011&query_hl=28&itool=pubmed_docsum

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PCR-induced sequence alterations hamper the typing of prehistoric bone samples for diagnostic achondroplasia mutations. Author(s): Pusch CM, Broghammer M, Nicholson GJ, Nerlich AG, Zink A, Kennerknecht I, Bachmann L, Blin N. Source: Molecular Biology and Evolution. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15254256&query_hl=28&itool=pubmed_docsum

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Pediatric patients with achondroplasia: CT evaluation of the craniocervical junction. Author(s): Wang H, Rosenbaum AE, Reid CS, Zinreich SJ, Pyeritz RE. Source: Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3602395&query_hl=28&itool=pubmed_docsum

Studies

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Perioperative intracranial hemorrhage in achondroplasia: a case report. Author(s): Elmaci I, Ain MC, Wright MJ, Lee RR, Sheppard JM, Rigamonti D, Hurko O. Source: Journal of Neurosurgical Anesthesiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10905569&query_hl=28&itool=pubmed_docsum

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Polycystic kidney disease in a patient with achondroplasia: case report. Author(s): McLigeyo SO, Kisiangani GS. Source: East Afr Med J. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12755243&query_hl=28&itool=pubmed_docsum

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Polyhydramnios: a predictor of severe growth impairment in achondroplasia. Author(s): Latini G, De Felice C, Parrini S, Verrotti A, Di Maggio G, Petraglia F. Source: The Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12183727&query_hl=28&itool=pubmed_docsum

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Posterior fossa decompression without duraplasty in infants and young children for treatment of Chiari malformation and achondroplasia. Author(s): Yundt KD, Park TS, Tantuwaya VS, Kaufman BA. Source: Pediatric Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9309784&query_hl=28&itool=pubmed_docsum

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Posterior osteotomy and instrumentation for thoracolumbar kyphosis in patients with achondroplasia. Author(s): Qi X, Matsumoto M, Ishii K, Nakamura M, Chiba K, Toyama Y. Source: Spine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16924200&query_hl=28&itool=pubmed_docsum

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Prediction of the growth in patients with achondroplasia. Author(s): Zemkova D, Krasnicanova H, Marik I. Source: Arztl Jugendkd. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=1759634&query_hl=28&itool=pubmed_docsum

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Predominance of the mutation at 1138 of the cDNA for the fibroblast growth factor receptor 3 in Japanese patients with achondroplasia. Author(s): Tonoki H, Nakae J, Tajima T, Shinohara N, Monji J, Satoh S, Fujieda K. Source: Jpn J Hum Genet. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8851771&query_hl=28&itool=pubmed_docsum

Achondroplasia

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Preimplantation genetic diagnosis for achondroplasia: genetics and gynaecological limits and difficulties. Author(s): Moutou C, Rongieres C, Bettahar-Lebugle K, Gardes N, Philippe C, Viville S. Source: Human Reproduction (Oxford, England). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12615816&query_hl=28&itool=pubmed_docsum

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Premutation in achondroplasia. Author(s): Opitz JM. Source: Basic Life Sci. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3240248&query_hl=28&itool=pubmed_docsum

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Prenatal diagnosis of achondroplasia presenting with multiple-suture synostosis: a novel association. Author(s): Karadimas C, Trouvas D, Haritatos G, Makatsoris C, Dedoulis E, Velissariou V, Antoniadi T, Hatzaki A, Petersen MB. Source: Prenatal Diagnosis. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16475234&query_hl=28&itool=pubmed_docsum

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Prenatal diagnosis of achondroplasia using the nested polymerase chain reaction with modified primer sets. Author(s): Sawai H, Komori S, Tanaka H, Bessho T, Koyama K. Source: Fetal Diagnosis and Therapy. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9115628&query_hl=28&itool=pubmed_docsum

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Prenatal diagnosis of achondroplasia. Author(s): Chakraborty RK, Mahmood S, Hossain GA, Akhter N, Akhter M. Source: Mymensingh Med J. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15284703&query_hl=28&itool=pubmed_docsum

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Prenatal diagnosis of the Turner syndrome, a familial chromosomal rearrangement and achondroplasia by amniocentesis and ultrasonography. Author(s): Leonard CO, Sanders RC, Lau HL. Source: Johns Hopkins Med J. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=87533&query_hl=28&itool=pubmed_docsum

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Prenatal ultrasonographic demonstration of the trident hand in heterozygous achondroplasia. Author(s): Guzman ER, Day-Salvatore D, Westover T, Rosenberg JC, Beim D, Grabelle H. Source: Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7636958&query_hl=28&itool=pubmed_docsum

Studies

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Presumed hom*ozygous achondroplasia. A review and report of a further case. Author(s): Aterman K, Welch JP, Taylor PG. Source: Pathology, Research and Practice. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=6359101&query_hl=28&itool=pubmed_docsum

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Prevention of fixed, angular kyphosis in achondroplasia. Author(s): Pauli RM, Breed A, Horton VK, Glinski LP, Reiser CA. Source: Journal of Pediatric Orthopedics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9591973&query_hl=28&itool=pubmed_docsum

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Prospective assessment of risks for cervicomedullary-junction compression in infants with achondroplasia. Author(s): Pauli RM, Horton VK, Glinski LP, Reiser CA. Source: American Journal of Human Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7887429&query_hl=28&itool=pubmed_docsum

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Radiographic features of the bones of the hand and wrist in achondroplasia: report of case. Author(s): So LL, King NM. Source: Asdc J Dent Child. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=1939806&query_hl=28&itool=pubmed_docsum

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Radiologic features of achondroplasia. Author(s): Silverman FN. Source: Basic Life Sci. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3240266&query_hl=28&itool=pubmed_docsum

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Rapid combined genotyping assay for four achondroplasia and hypochondroplasia mutations by real-time PCR with multiple detection probes. Author(s): Schrijver I, Lay MJ, Zehnder JL. Source: Genetic Testing. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15345118&query_hl=28&itool=pubmed_docsum

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Rapid detection of FGFR3 gene mutation in achondroplasia by DHPLC systemcoupling heteroduplex and fluorescence-enhanced primer-extension analysis. Author(s): Su YN, Lee CN, Chien SC, Hung CC, Chien YH, Chen CA. Source: Journal of Human Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15221641&query_hl=28&itool=pubmed_docsum

Achondroplasia

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Recent milestones in achondroplasia research. Author(s): Horton WA. Source: Am J Med Genet A. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16353253&query_hl=28&itool=pubmed_docsum

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Recurrence risk for sibs of children with "sporadic" achondroplasia. Author(s): Mettler G, Fraser FC. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10678665&query_hl=28&itool=pubmed_docsum

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Relevant principles in the management of spinal disorders in achondroplasia. Author(s): O'Brien JP, Mehdian H. Source: Basic Life Sci. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3240264&query_hl=28&itool=pubmed_docsum

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Reoperation for spinal restenosis in achondroplasia. Author(s): Ain MC, Elmaci I, Hurko O, Clatterbuck RE, Lee RR, Rigamonti D. Source: Journal of Spinal Disorders. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10780694&query_hl=28&itool=pubmed_docsum

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Respiratory complications of achondroplasia. Author(s): Stokes DC, Phillips JA, Leonard CO, Dorst JP, Kopits SE, Trojak JE, Brown DL. Source: The Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=6834188&query_hl=28&itool=pubmed_docsum

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Reversibility of deficient sleep entrained growth hormone secretion in a boy with achondroplasia and obstructive sleep apnea. Author(s): Goldstein SJ, Wu RH, Thorpy MJ, Shprintzen RJ, Marion RE, Saenger P. Source: Acta Endocrinol (Copenh). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3661058&query_hl=28&itool=pubmed_docsum

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Sagging rope sign in achondroplasia is different from Perthes disease. Author(s): Oh CW, Shingade VU, Song HR, Suh SW, Hong JS, Lee SH. Source: Journal of Pediatric Orthopedics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16294124&query_hl=28&itool=pubmed_docsum

Studies

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Severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN): phenotypic analysis of a new skeletal dysplasia caused by a Lys650Met mutation in fibroblast growth factor receptor 3. Author(s): Bellus GA, Bamshad MJ, Przylepa KA, Dorst J, Lee RR, Hurko O, Jabs EW, Curry CJ, Wilcox WR, Lachman RS, Rimoin DL, Francomano CA. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10377013&query_hl=28&itool=pubmed_docsum

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Severe complications in a child with achondroplasia and two FGFR3 mutations on the same allele. Author(s): Rump P, Letteboer TG, Gille JJ, Torringa MJ, Baerts W, van Gestel JP, Verheij JB, van Essen AJ. Source: Am J Med Genet A. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16411219&query_hl=28&itool=pubmed_docsum

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Severe pulmonary hypertension in an infant with achondroplasia. Author(s): Ito T, Sawaishi Y, Ito Y, Sugawara A. Source: Lancet. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11589938&query_hl=28&itool=pubmed_docsum

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Short-term recombinant human growth hormone treatment increases growth rate in achondroplasia. Author(s): Shohat M, Tick D, Barakat S, Bu X, Melmed S, Rimoin DL. Source: The Journal of Clinical Endocrinology and Metabolism. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8923856&query_hl=28&itool=pubmed_docsum

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Skeletal development of achondroplasia: analysis of genotyped patients. Author(s): Matsui Y, Kawabata H, Ozono K, Yasui N. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11472579&query_hl=28&itool=pubmed_docsum

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Sleep and upper airway obstruction in children with achondroplasia. Author(s): Zucconi M, Weber G, Castronovo V, Ferini-Strambi L, Russo F, Chiumello G, Smirne S. Source: The Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8917243&query_hl=28&itool=pubmed_docsum

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Sleep disordered breathing in children with achondroplasia. Part 2. Relationship with craniofacial and airway morphology. Author(s): Onodera K, Niikuni N, Chigono T, Nakajima I, Sakata H, Motizuki H. Source: International Journal of Pediatric Otorhinolaryngology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16406083&query_hl=28&itool=pubmed_docsum

Achondroplasia

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Sleep-disordered breathing in children with achondroplasia. Author(s): Mogayzel PJ Jr, Carroll JL, Loughlin GM, Hurko O, Francomano CA, Marcus CL. Source: The Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9580768&query_hl=28&itool=pubmed_docsum

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Spinal arthrodesis with instrumentation for thoracolumbar kyphosis in pediatric achondroplasia. Author(s): Ain MC, Browne JA. Source: Spine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15371713&query_hl=28&itool=pubmed_docsum

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Spinal compression in achondroplasia. Author(s): Hanco*ck DO, Philips DG. Source: Paraplegia. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=5829900&query_hl=28&itool=pubmed_docsum

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Spinal fusion for kyphosis in achondroplasia. Author(s): Ain MC, Shirley ED. Source: Journal of Pediatric Orthopedics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15308905&query_hl=28&itool=pubmed_docsum

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Standard weight for height curves in achondroplasia. Author(s): Hunter AG, Hecht JT, Scott CI Jr. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8882783&query_hl=28&itool=pubmed_docsum

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Subtle radiographic findings of achondroplasia in patients with Crouzon syndrome with acanthosis nigricans due to an Ala391Glu substitution in FGFR3. Author(s): Schweitzer DN, Graham JM Jr, Lachman RS, Jabs EW, Okajima K, Przylepa KA, Shanske A, Chen K, Neidich JA, Wilcox WR. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11426459&query_hl=28&itool=pubmed_docsum

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Surgical correction of bowlegs in achondroplasia. Author(s): Beals RK, Stanley G. Source: Journal of Pediatric Orthopaedics. Part B / European Paediatric Orthopaedic Society, Pediatric Orthopaedic Society of North America. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15931026&query_hl=28&itool=pubmed_docsum

Studies

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Surgical management of cervicomedullary compression in achondroplasia. Author(s): Yamada Y, Ito H, Otsubo Y, Sekido K. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9118140&query_hl=28&itool=pubmed_docsum

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Surgical treatment of achondroplasia with thoracolumbar kyphosis and spinal stenosis--a case report. Author(s): Liao JC, Chen WJ, Lai PL, Chen LH. Source: Acta Orthop. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16819698&query_hl=28&itool=pubmed_docsum

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Surgical treatment of lumbar stenosis in achondroplasia. Author(s): Thomeer RT, van Dijk JM. Source: Journal of Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11990837&query_hl=28&itool=pubmed_docsum

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Survey of the present status of sleep-disordered breathing in children with achondroplasia Part I. A questionnaire survey. Author(s): Onodera K, Sakata H, Niikuni N, Nonaka T, Kobayashi K, Nakajima I. Source: International Journal of Pediatric Otorhinolaryngology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15763281&query_hl=28&itool=pubmed_docsum

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Syndrome of incomplete regional achondroplasia (ilium and ribs) with abdominal muscle dysplasia. Author(s): Shapira E, Fischel E, Moses S, Levin S. Source: Archives of Disease in Childhood. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=4221179&query_hl=28&itool=pubmed_docsum

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The achondroplasia mutation does not alter the dimerization energetics of the fibroblast growth factor receptor 3 transmembrane domain. Author(s): You M, Li E, Hristova K. Source: Biochemistry. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16634636&query_hl=28&itool=pubmed_docsum

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The comparison of the effects of short-term growth hormone treatment in patients with achondroplasia and with hypochondroplasia. Author(s): Tanaka N, Katsumata N, Horikawa R, Tanaka T. Source: Endocrine Journal. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12733711&query_hl=28&itool=pubmed_docsum

Achondroplasia

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The diameter of callus in leg lengthening: 28 tibial lengthenings in 14 patients with achondroplasia. Author(s): Mamada K, Nakamura K, Matsush*ta T, Okazaki H, Shiro R, Ou W, Tanaka K, Kurokawa T. Source: Acta Orthopaedica Scandinavica. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9703409&query_hl=28&itool=pubmed_docsum

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The gene for achondroplasia maps to the telomeric region of chromosome 4p. Author(s): Velinov M, Slaugenhaupt SA, Stoilov I, Scott CI Jr, Gusella JF, Tsipouras P. Source: Nature Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8012397&query_hl=28&itool=pubmed_docsum

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The molecular and genetic basis of fibroblast growth factor receptor 3 disorders: the achondroplasia family of skeletal dysplasias, Muenke craniosynostosis, and Crouzon syndrome with acanthosis nigricans. Author(s): Vajo Z, Francomano CA, Wilkin DJ. Source: Endocrine Reviews. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10696568&query_hl=28&itool=pubmed_docsum

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The neurological complications of achondroplasia. Author(s): Gordon N. Source: Brain & Development. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10761826&query_hl=28&itool=pubmed_docsum

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The observed human sperm mutation frequency cannot explain the achondroplasia paternal age effect. Author(s): Tiemann-Boege I, Navidi W, Grewal R, Cohn D, Eskenazi B, Wyrobek AJ, Arnheim N. Source: Proceedings of the National Academy of Sciences of the United States of America. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12397172&query_hl=28&itool=pubmed_docsum

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The prospective management of cervicomedullary compression in achondroplasia. Author(s): Thomas IT, Frias JL. Source: Birth Defects Orig Artic Ser. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2697385&query_hl=28&itool=pubmed_docsum

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The psychodynamics of achondroplasia. Author(s): Ancona L. Source: Basic Life Sci. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3240281&query_hl=28&itool=pubmed_docsum

Studies

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The role of endoscopic third ventriculostomy in the treatment of triventricular hydrocephalus seen in children with achondroplasia. Author(s): Etus V, Ceylan S. Source: Journal of Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16238080&query_hl=28&itool=pubmed_docsum

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The surgical treatment of vertebral deformities in achondroplastic dwarfism. Author(s): Parisini P, Greggi T, Casadei R, Martini A, De Zerbi M, Campanacci L, Perozzi M. Source: Chir Organi Mov. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8968116&query_hl=29&itool=pubmed_docsum

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The use of gated cine phase contrast and MR venography in achondroplasia. Author(s): Rollins N, Booth T, Shapiro K. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11048631&query_hl=28&itool=pubmed_docsum

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Therapy-resistant papilledema in achondroplasia. Author(s): Landau K, Gloor BP. Source: Journal of Neuro-Ophthalmology : the Official Journal of the North American Neuro-Ophthalmology Society. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8032476&query_hl=28&itool=pubmed_docsum

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Thoracolumbar spinal deformity in achondroplasia. Author(s): Misra SN, Morgan HW. Source: Neurosurg Focus. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15766221&query_hl=28&itool=pubmed_docsum

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Three-dimensional sonographic aspects in the antenatal diagnosis of achondroplasia. Author(s): Moeglin D, Benoit B. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11489233&query_hl=28&itool=pubmed_docsum

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Treatment of achondroplasia with growth hormone: six years of experience. Author(s): Ramaswami U, Rumsby G, Spoudeas HA, Hindmarsh PC, Brook CG. Source: Pediatric Research. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10509364&query_hl=28&itool=pubmed_docsum

Achondroplasia

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Treatment of kyphosis and lumbar stenosis in achondroplasia. Author(s): Lonstein JE. Source: Basic Life Sci. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3240263&query_hl=28&itool=pubmed_docsum

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Treatment of obstructive sleep apnea in achondroplasia: evaluation of sleep, breathing, and somatosensory-evoked potentials. Author(s): Waters KA, Everett F, Sillence DO, fa*gan ER, Sullivan CE. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8585566&query_hl=28&itool=pubmed_docsum

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Trigeminal neuralgia associated with achondroplasia. Case report with literature review. Author(s): Takada Y, Morimoto T, Sugawara T, Ohno K. Source: Acta Neurochirurgica. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11731870&query_hl=28&itool=pubmed_docsum

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Two sibs who are double heterozygotes for achondroplasia and pseudoachondroplastic dysplasia. Author(s): Woods CG, Rogers JG, Mayne V. Source: Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7966194&query_hl=28&itool=pubmed_docsum

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Ultrasonographic features in a case of heterozygous achondroplasia at 25 weeks' gestation. Author(s): Cordone M, Lituania M, Bocchino G, Passamonti U, Toma P, Camera G. Source: Prenatal Diagnosis. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8341638&query_hl=28&itool=pubmed_docsum

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Ultrasound and molecular mid-trimester prenatal diagnosis of de novo achondroplasia. Author(s): Mesoraca A, Pilu G, Perolo A, Novelli G, Salfi N, Lucchi A, Bovicelli L, Dallapiccola B. Source: Prenatal Diagnosis. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8878289&query_hl=28&itool=pubmed_docsum

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Unexpected death of children with achondroplasia after the perinatal period. Author(s): Bland JD, Emery JL. Source: Developmental Medicine and Child Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7117707&query_hl=28&itool=pubmed_docsum

Studies

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Upper cervical myelopathy in achondroplasia. Author(s): Yang SS, Corbett DP, Brough AJ, Heidelberger KP, Bernstein J. Source: American Journal of Clinical Pathology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=868806&query_hl=28&itool=pubmed_docsum

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Urine leakage from the umbilicus in a child with achondroplasia and tetraplegia (due to cervical stenosis): a safety vent for the obstructed neuropathic bladder. Author(s): Krishnan KR, Vaidyanathan S, Soni BM, Watt JW. Source: International Urology and Nephrology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9203037&query_hl=28&itool=pubmed_docsum

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Variation of quantitative and qualitative changes of enchondral ossification in heterozygous achondroplasia. Author(s): Briner J, Giedion A, Spycher MA. Source: Pathology, Research and Practice. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=1906169&query_hl=28&itool=pubmed_docsum

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Vascular malformations of the brain in achondroplasia. Case report. Author(s): Pau A, Orunesu G. Source: Acta Neurochirurgica. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=517198&query_hl=28&itool=pubmed_docsum

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Ventricular size and intelligence in achondroplasia. Author(s): Priestley BL, Lorber J. Source: Z Kinderchir. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7331541&query_hl=28&itool=pubmed_docsum

CHAPTER 2. ALTERNATIVE MEDICINE AND ACHONDROPLASIA Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to achondroplasia. At the conclusion of this chapter, we will provide additional sources.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to achondroplasia and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select CAM on PubMed. Enter achondroplasia (or synonyms) into the search box. Click Go. The following references provide information on particular aspects of complementary and alternative medicine that are related to achondroplasia: •

Achondroplasia. Author(s): Castiglia PT. Source: Journal of Pediatric Health Care : Official Publication of National Association of Pediatric Nurse Associates & Practitioners. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8920380&query_hl=1&itool=pubmed_docsum

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Complementary antagonistic actions between C-type natriuretic peptide and the MAPK pathway through FGFR-3 in ATDC5 cells. Author(s): Ozasa A, Komatsu Y, Yasoda A, Miura M, Sakuma Y, Nakatsuru Y, Arai H, Itoh N, Nakao K. Source: Bone. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15869918&query_hl=1&itool=pubmed_docsum

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Delineation of facial archetypes by 3d averaging. Author(s): Shaweesh AI, Thomas CD, Bankier A, Clement JG. Source: Ann R Australas Coll Dent Surg. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16479861&query_hl=1&itool=pubmed_docsum

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Diastrophic dwarfism in early infancy. Author(s): LANGER LO Jr. Source: Am J Roentgenol Radium Ther Nucl Med. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=14258290&query_hl=1&itool=pubmed_docsum

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Dwarfism in the amish. ii. cartilage-hair hypoplasia. Author(s): MCKUSICK VA, ELDRIDGE R, HOSTETLER JA, RUANGWIT U, EGELAND JA. Source: Bull Johns Hopkins Hosp. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=14284412&query_hl=1&itool=pubmed_docsum

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Little People of America: position statement on genetic discoveries in dwarfism (1996). Author(s): Ricker R. Source: Genetic Resour. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12731507&query_hl=1&itool=pubmed_docsum

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Pediatric neurology. Author(s): Baird HW. Source: Prog Neurol Psychiatry. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=4977707&query_hl=1&itool=pubmed_docsum

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Transplantation of marrow-derived mesenchymal stem cells and platelet-rich plasma during distraction osteogenesis--a preliminary result of three cases. Author(s): Kitoh H, Kitakoji T, Tsuchiya H, Mitsuyama H, Nakamura H, Katoh M, Ishiguro N. Source: Bone. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15454096&query_hl=1&itool=pubmed_docsum

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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AOL: http://health.aol.com/healthyliving/althealth

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com®: http://www.drkoop.com/naturalmedicine.html

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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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Google: http://directory.google.com/Top/Health/Alternative/

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Healthnotes: http://www.healthnotes.com/

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Open Directory Project: http://dmoz.org/Health/Alternative/

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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

APPENDICES

APPENDIX A. HELP ME UNDERSTAND GENETICS Overview This appendix presents basic information about genetics in clear language and provides links to online resources.7

The Basics: Genes and How They Work This section gives you information on the basics of cells, DNA, genes, chromosomes, and proteins. What Is a Cell? Cells are the basic building blocks of all living things. The human body is composed of trillions of cells. They provide structure for the body, take in nutrients from food, convert those nutrients into energy, and carry out specialized functions. Cells also contain the body’s hereditary material and can make copies of themselves. Cells have many parts, each with a different function. Some of these parts, called organelles, are specialized structures that perform certain tasks within the cell. Human cells contain the following major parts, listed in alphabetical order: •

Cytoplasm: The cytoplasm is fluid inside the cell that surrounds the organelles.

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Endoplasmic reticulum (ER): This organelle helps process molecules created by the cell and transport them to their specific destinations either inside or outside the cell.

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Golgi apparatus: The golgi apparatus packages molecules processed by the endoplasmic reticulum to be transported out of the cell.

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Lysosomes and peroxisomes: These organelles are the recycling center of the cell. They digest foreign bacteria that invade the cell, rid the cell of toxic substances, and recycle worn-out cell components.

This appendix is an excerpt from the National Library of Medicine’s handbook, Help Me Understand Genetics. For the full text of the Help Me Understand Genetics handbook, see http://ghr.nlm.nih.gov/handbook.

Help Me Understand Genetics

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Mitochondria: Mitochondria are complex organelles that convert energy from food into a form that the cell can use. They have their own genetic material, separate from the DNA in the nucleus, and can make copies of themselves.

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Nucleus: The nucleus serves as the cell’s command center, sending directions to the cell to grow, mature, divide, or die. It also houses DNA (deoxyribonucleic acid), the cell’s hereditary material. The nucleus is surrounded by a membrane called the nuclear envelope, which protects the DNA and separates the nucleus from the rest of the cell.

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Plasma membrane: The plasma membrane is the outer lining of the cell. It separates the cell from its environment and allows materials to enter and leave the cell.

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Ribosomes: Ribosomes are organelles that process the cell’s genetic instructions to create proteins. These organelles can float freely in the cytoplasm or be connected to the endoplasmic reticulum. What Is DNA?

DNA, or deoxyribonucleic acid, is the hereditary material in humans and almost all other organisms. Nearly every cell in a person’s body has the same DNA. Most DNA is located in the cell nucleus (where it is called nuclear DNA), but a small amount of DNA can also be found in the mitochondria (where it is called mitochondrial DNA or mtDNA). The information in DNA is stored as a code made up of four chemical bases: adenine (A), guanine (G), cytosine (C), and thymine (T). Human DNA consists of about 3 billion bases, and more than 99 percent of those bases are the same in all people. The order, or sequence, of these bases determines the information available for building and maintaining an organism, similar to the way in which letters of the alphabet appear in a certain order to form words and sentences. DNA bases pair up with each other, A with T and C with G, to form units called base pairs. Each base is also attached to a sugar molecule and a phosphate molecule. Together, a base, sugar, and phosphate are called a nucleotide. Nucleotides are arranged in two long strands that form a spiral called a double helix. The structure of the double helix is somewhat like a ladder, with the base pairs forming the ladder’s rungs and the sugar and phosphate molecules forming the vertical sidepieces of the ladder. An important property of DNA is that it can replicate, or make copies of itself. Each strand of DNA in the double helix can serve as a pattern for duplicating the sequence of bases. This is critical when cells divide because each new cell needs to have an exact copy of the DNA present in the old cell.

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DNA is a double helix formed by base pairs attached to a sugar-phosphate backbone. What Is Mitochondrial DNA? Although most DNA is packaged in chromosomes within the nucleus, mitochondria also have a small amount of their own DNA. This genetic material is known as mitochondrial DNA or mtDNA. Mitochondria are structures within cells that convert the energy from food into a form that cells can use. Each cell contains hundreds to thousands of mitochondria, which are located in the fluid that surrounds the nucleus (the cytoplasm). Mitochondria produce energy through a process called oxidative phosphorylation. This process uses oxygen and simple sugars to create adenosine triphosphate (ATP), the cell’s main energy source. A set of enzyme complexes, designated as complexes I-V, carry out oxidative phosphorylation within mitochondria. In addition to energy production, mitochondria play a role in several other cellular activities. For example, mitochondria help regulate the self-destruction of cells (apoptosis). They are also necessary for the production of substances such as cholesterol and heme (a component of hemoglobin, the molecule that carries oxygen in the blood). Mitochondrial DNA contains 37 genes, all of which are essential for normal mitochondrial function. Thirteen of these genes provide instructions for making enzymes involved in oxidative phosphorylation. The remaining genes provide instructions for making molecules called transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs), which are chemical cousins of

Help Me Understand Genetics

DNA. These types of RNA help assemble protein building blocks (amino acids) into functioning proteins. What Is a Gene? A gene is the basic physical and functional unit of heredity. Genes, which are made up of DNA, act as instructions to make molecules called proteins. In humans, genes vary in size from a few hundred DNA bases to more than 2 million bases. The Human Genome Project has estimated that humans have between 20,000 and 25,000 genes. Every person has two copies of each gene, one inherited from each parent. Most genes are the same in all people, but a small number of genes (less than 1 percent of the total) are slightly different between people. Alleles are forms of the same gene with small differences in their sequence of DNA bases. These small differences contribute to each person’s unique physical features.

Genes are made up of DNA. Each chromosome contains many genes. What Is a Chromosome? In the nucleus of each cell, the DNA molecule is packaged into thread-like structures called chromosomes. Each chromosome is made up of DNA tightly coiled many times around proteins called histones that support its structure. Chromosomes are not visible in the cell’s nucleus—not even under a microscope—when the cell is not dividing. However, the DNA that makes up chromosomes becomes more tightly packed during cell division and is then visible under a microscope. Most of what researchers know about chromosomes was learned by observing chromosomes during cell division. Each chromosome has a constriction point called the centromere, which divides the chromosome into two sections, or “arms.” The short arm of the chromosome is labeled the “p arm.” The long arm of the chromosome is labeled the “q arm.” The location of the centromere on each chromosome gives the chromosome its characteristic shape, and can be used to help describe the location of specific genes.

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DNA and histone proteins are packaged into structures called chromosomes. How Many Chromosomes Do People Have? In humans, each cell normally contains 23 pairs of chromosomes, for a total of 46. Twentytwo of these pairs, called autosomes, look the same in both males and females. The 23rd pair, the sex chromosomes, differ between males and females. Females have two copies of the X chromosome, while males have one X and one Y chromosome.

Help Me Understand Genetics

The 22 autosomes are numbered by size. The other two chromosomes, X and Y, are the sex chromosomes. This picture of the human chromosomes lined up in pairs is called a karyotype. How Do Geneticists Indicate the Location of a Gene? Geneticists use maps to describe the location of a particular gene on a chromosome. One type of map uses the cytogenetic location to describe a gene’s position. The cytogenetic location is based on a distinctive pattern of bands created when chromosomes are stained with certain chemicals. Another type of map uses the molecular location, a precise description of a gene’s position on a chromosome. The molecular location is based on the sequence of DNA building blocks (base pairs) that make up the chromosome. Cytogenetic Location Geneticists use a standardized way of describing a gene’s cytogenetic location. In most cases, the location describes the position of a particular band on a stained chromosome: 17q12 It can also be written as a range of bands, if less is known about the exact location: 17q12-q21 The combination of numbers and letters provide a gene’s “address” on a chromosome. This address is made up of several parts: •

The chromosome on which the gene can be found. The first number or letter used to describe a gene’s location represents the chromosome. Chromosomes 1 through 22 (the autosomes) are designated by their chromosome number. The sex chromosomes are designated by X or Y.

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The arm of the chromosome. Each chromosome is divided into two sections (arms) based on the location of a narrowing (constriction) called the centromere. By convention, the shorter arm is called p, and the longer arm is called q. The chromosome arm is the second part of the gene’s address. For example, 5q is the long arm of chromosome 5, and Xp is the short arm of the X chromosome.

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The position of the gene on the p or q arm. The position of a gene is based on a distinctive pattern of light and dark bands that appear when the chromosome is stained in a certain way. The position is usually designated by two digits (representing a region and a band), which are sometimes followed by a decimal point and one or more additional digits (representing sub-bands within a light or dark area). The number indicating the gene position increases with distance from the centromere. For example: 14q21 represents position 21 on the long arm of chromosome 14. 14q21 is closer to the centromere than 14q22.

Sometimes, the abbreviations “cen” or “ter” are also used to describe a gene’s cytogenetic location. “Cen” indicates that the gene is very close to the centromere. For example, 16pcen refers to the short arm of chromosome 16 near the centromere. “Ter” stands for terminus, which indicates that the gene is very close to the end of the p or q arm. For example, 14qter refers to the tip of the long arm of chromosome 14. (“Tel” is also sometimes used to describe a gene’s location. “Tel” stands for telomeres, which are at the ends of each chromosome. The abbreviations “tel” and “ter” refer to the same location.)

The CFTR gene is located on the long arm of chromosome 7 at position 7q31.2.

Help Me Understand Genetics

Molecular Location The Human Genome Project, an international research effort completed in 2003, determined the sequence of base pairs for each human chromosome. This sequence information allows researchers to provide a more specific address than the cytogenetic location for many genes. A gene’s molecular address pinpoints the location of that gene in terms of base pairs. For example, the molecular location of the APOE gene on chromosome 19 begins with base pair 50,100,901 and ends with base pair 50,104,488. This range describes the gene’s precise position on chromosome 19 and indicates the size of the gene (3,588 base pairs). Knowing a gene’s molecular location also allows researchers to determine exactly how far the gene is from other genes on the same chromosome. Different groups of researchers often present slightly different values for a gene’s molecular location. Researchers interpret the sequence of the human genome using a variety of methods, which can result in small differences in a gene’s molecular address. For example, the National Center for Biotechnology Information (NCBI) identifies the molecular location of the APOE gene as base pair 50,100,901 to base pair 50,104,488 on chromosome 19. The Ensembl database identifies the location of this gene as base pair 50,100,879 to base pair 50,104,489 on chromosome 19. Neither of these addresses is incorrect; they represent different interpretations of the same data. For consistency, Genetics Home Reference presents data from NCBI for the molecular location of genes. What Are Proteins and What Do They Do? Proteins are large, complex molecules that play many critical roles in the body. They do most of the work in cells and are required for the structure, function, and regulation of the body’s tissues and organs. Proteins are made up of hundreds or thousands of smaller units called amino acids, which are attached to one another in long chains. There are 20 different types of amino acids that can be combined to make a protein. The sequence of amino acids determines each protein’s unique 3-dimensional structure and its specific function.

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Examples of Protein Functions Proteins can be described according to their large range of functions in the body, listed in alphabetical order: Function Antibody

Description Antibodies bind to specific foreign particles, such as viruses and bacteria, to help protect the body.

Example Immunoglobulin G (IgG)

Enzyme

Enzymes carry out almost all of the thousands of chemical reactions that take place in cells. They also assist with the formation of new molecules by reading the genetic information stored in DNA.

Phenylalanine hydroxylase

Messenger

Messenger proteins, such as some types of hormones, transmit signals to coordinate biological processes between different cells, tissues, and organs.

Growth hormone

Structural component

These proteins provide structure and support for cells. On a larger scale, they also allow the body to move. These proteins bind and carry atoms and small molecules within cells and throughout the body.

Actin

Transport/storage

Ferritin

How Does a Gene Make a Protein? Most genes contain the information needed to make functional molecules called proteins. (A few genes produce other molecules that help the cell assemble proteins.) The journey from gene to protein is complex and tightly controlled within each cell. It consists of two major steps: transcription and translation. Together, transcription and translation are known as gene expression. During the process of transcription, the information stored in a gene’s DNA is transferred to a similar molecule called RNA (ribonucleic acid) in the cell nucleus. Both RNA and DNA are made up of a chain of nucleotide bases, but they have slightly different chemical properties. The type of RNA that contains the information for making a protein is called messenger RNA (mRNA) because it carries the information, or message, from the DNA out of the nucleus into the cytoplasm. Translation, the second step in getting from a gene to a protein, takes place in the cytoplasm. The mRNA interacts with a specialized complex called a ribosome, which “reads” the sequence of mRNA bases. Each sequence of three bases, called a codon, usually codes for

Help Me Understand Genetics

one particular amino acid. (Amino acids are the building blocks of proteins.) A type of RNA called transfer RNA (tRNA) assembles the protein, one amino acid at a time. Protein assembly continues until the ribosome encounters a “stop” codon (a sequence of three bases that does not code for an amino acid). The flow of information from DNA to RNA to proteins is one of the fundamental principles of molecular biology. It is so important that it is sometimes called the “central dogma.”

Through the processes of transcription and translation, information from genes is used to make proteins.

Can Genes Be Turned On and Off in Cells? Each cell expresses, or turns on, only a fraction of its genes. The rest of the genes are repressed, or turned off. The process of turning genes on and off is known as gene regulation. Gene regulation is an important part of normal development. Genes are turned on and off in different patterns during development to make a brain cell look and act different from a liver cell or a muscle cell, for example. Gene regulation also allows cells to react quickly to changes in their environments. Although we know that the regulation of genes is critical for life, this complex process is not yet fully understood. Gene regulation can occur at any point during gene expression, but most commonly occurs at the level of transcription (when the information in a gene’s DNA is transferred to mRNA). Signals from the environment or from other cells activate proteins called transcription factors. These proteins bind to regulatory regions of a gene and increase or decrease the level of transcription. By controlling the level of transcription, this process can determine the amount of protein product that is made by a gene at any given time.

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How Do Cells Divide? There are two types of cell division: mitosis and meiosis. Most of the time when people refer to “cell division,” they mean mitosis, the process of making new body cells. Meiosis is the type of cell division that creates egg and sperm cells. Mitosis is a fundamental process for life. During mitosis, a cell duplicates all of its contents, including its chromosomes, and splits to form two identical daughter cells. Because this process is so critical, the steps of mitosis are carefully controlled by a number of genes. When mitosis is not regulated correctly, health problems such as cancer can result. The other type of cell division, meiosis, ensures that humans have the same number of chromosomes in each generation. It is a two-step process that reduces the chromosome number by half—from 46 to 23—to form sperm and egg cells. When the sperm and egg cells unite at conception, each contributes 23 chromosomes so the resulting embryo will have the usual 46. Meiosis also allows genetic variation through a process of DNA shuffling while the cells are dividing.

Mitosis and meiosis, the two types of cell division. How Do Genes Control the Growth and Division of Cells? A variety of genes are involved in the control of cell growth and division. The cell cycle is the cell’s way of replicating itself in an organized, step-by-step fashion. Tight regulation of this process ensures that a dividing cell’s DNA is copied properly, any errors in the DNA are repaired, and each daughter cell receives a full set of chromosomes. The cycle has checkpoints (also called restriction points), which allow certain genes to check for mistakes and halt the cycle for repairs if something goes wrong.

Help Me Understand Genetics

If a cell has an error in its DNA that cannot be repaired, it may undergo programmed cell death (apoptosis). Apoptosis is a common process throughout life that helps the body get rid of cells it doesn’t need. Cells that undergo apoptosis break apart and are recycled by a type of white blood cell called a macrophage. Apoptosis protects the body by removing genetically damaged cells that could lead to cancer, and it plays an important role in the development of the embryo and the maintenance of adult tissues. Cancer results from a disruption of the normal regulation of the cell cycle. When the cycle proceeds without control, cells can divide without order and accumulate genetic defects that can lead to a cancerous tumor.

Genetic Mutations and Health This section presents basic information about gene mutations, chromosomal changes, and conditions that run in families.8 What Is a Gene Mutation and How Do Mutations Occur? A gene mutation is a permanent change in the DNA sequence that makes up a gene. Mutations range in size from a single DNA building block (DNA base) to a large segment of a chromosome. Gene mutations occur in two ways: they can be inherited from a parent or acquired during a person’s lifetime. Mutations that are passed from parent to child are called hereditary mutations or germline mutations (because they are present in the egg and sperm cells, which are also called germ cells). This type of mutation is present throughout a person’s life in virtually every cell in the body. Mutations that occur only in an egg or sperm cell, or those that occur just after fertilization, are called new (de novo) mutations. De novo mutations may explain genetic disorders in which an affected child has a mutation in every cell, but has no family history of the disorder. Acquired (or somatic) mutations occur in the DNA of individual cells at some time during a person’s life. These changes can be caused by environmental factors such as ultraviolet radiation from the sun, or can occur if a mistake is made as DNA copies itself during cell division. Acquired mutations in somatic cells (cells other than sperm and egg cells) cannot be passed on to the next generation. Mutations may also occur in a single cell within an early embryo. As all the cells divide during growth and development, the individual will have some cells with the mutation and some cells without the genetic change. This situation is called mosaicism. Some genetic changes are very rare; others are common in the population. Genetic changes that occur in more than 1 percent of the population are called polymorphisms. They are common enough to be considered a normal variation in the DNA. Polymorphisms are 8

This section has been adapted from the National Library of Medicine’s handbook, Help Me Understand Genetics, which presents basic information about genetics in clear language and provides links to online resources: http://ghr.nlm.nih.gov/handbook.

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responsible for many of the normal differences between people such as eye color, hair color, and blood type. Although many polymorphisms have no negative effects on a person’s health, some of these variations may influence the risk of developing certain disorders. How Can Gene Mutations Affect Health and Development? To function correctly, each cell depends on thousands of proteins to do their jobs in the right places at the right times. Sometimes, gene mutations prevent one or more of these proteins from working properly. By changing a gene’s instructions for making a protein, a mutation can cause the protein to malfunction or to be missing entirely. When a mutation alters a protein that plays a critical role in the body, it can disrupt normal development or cause a medical condition. A condition caused by mutations in one or more genes is called a genetic disorder. In some cases, gene mutations are so severe that they prevent an embryo from surviving until birth. These changes occur in genes that are essential for development, and often disrupt the development of an embryo in its earliest stages. Because these mutations have very serious effects, they are incompatible with life. It is important to note that genes themselves do not cause disease—genetic disorders are caused by mutations that make a gene function improperly. For example, when people say that someone has “the cystic fibrosis gene,” they are usually referring to a mutated version of the CFTR gene, which causes the disease. All people, including those without cystic fibrosis, have a version of the CFTR gene. Do All Gene Mutations Affect Health and Development? No, only a small percentage of mutations cause genetic disorders—most have no impact on health or development. For example, some mutations alter a gene’s DNA base sequence but do not change the function of the protein made by the gene. Often, gene mutations that could cause a genetic disorder are repaired by certain enzymes before the gene is expressed (makes a protein). Each cell has a number of pathways through which enzymes recognize and repair mistakes in DNA. Because DNA can be damaged or mutated in many ways, DNA repair is an important process by which the body protects itself from disease. A very small percentage of all mutations actually have a positive effect. These mutations lead to new versions of proteins that help an organism and its future generations better adapt to changes in their environment. For example, a beneficial mutation could result in a protein that protects the organism from a new strain of bacteria. For More Information about DNA Repair and the Health Effects of Gene Mutations •

The University of Utah Genetic Science Learning Center provides information about genetic disorders that explains why some mutations cause disorders but others do not. (Refer to the questions in the far right column.) See http://learn.genetics.utah.edu/units/disorders/whataregd/.

Help Me Understand Genetics

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Additional information about DNA repair is available from the NCBI Science Primer. In the chapter called “What Is A Cell?”, scroll down to the heading “DNA Repair Mechanisms.” See http://www.ncbi.nlm.nih.gov/About/primer/genetics_cell.html. What Kinds of Gene Mutations Are Possible?

The DNA sequence of a gene can be altered in a number of ways. Gene mutations have varying effects on health, depending on where they occur and whether they alter the function of essential proteins. The types of mutations include: •

Missense mutation: This type of mutation is a change in one DNA base pair that results in the substitution of one amino acid for another in the protein made by a gene.

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Nonsense mutation: A nonsense mutation is also a change in one DNA base pair. Instead of substituting one amino acid for another, however, the altered DNA sequence prematurely signals the cell to stop building a protein. This type of mutation results in a shortened protein that may function improperly or not at all.

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Insertion: An insertion changes the number of DNA bases in a gene by adding a piece of DNA. As a result, the protein made by the gene may not function properly.

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Deletion: A deletion changes the number of DNA bases by removing a piece of DNA. Small deletions may remove one or a few base pairs within a gene, while larger deletions can remove an entire gene or several neighboring genes. The deleted DNA may alter the function of the resulting protein(s).

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Duplication: A duplication consists of a piece of DNA that is abnormally copied one or more times. This type of mutation may alter the function of the resulting protein.

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Frameshift mutation: This type of mutation occurs when the addition or loss of DNA bases changes a gene’s reading frame. A reading frame consists of groups of 3 bases that each code for one amino acid. A frameshift mutation shifts the grouping of these bases and changes the code for amino acids. The resulting protein is usually nonfunctional. Insertions, deletions, and duplications can all be frameshift mutations.

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Repeat expansion: Nucleotide repeats are short DNA sequences that are repeated a number of times in a row. For example, a trinucleotide repeat is made up of 3-base-pair sequences, and a tetranucleotide repeat is made up of 4-base-pair sequences. A repeat expansion is a mutation that increases the number of times that the short DNA sequence is repeated. This type of mutation can cause the resulting protein to function improperly. Can Changes in Chromosomes Affect Health and Development?

Changes that affect entire chromosomes or segments of chromosomes can cause problems with growth, development, and function of the body’s systems. These changes can affect many genes along the chromosome and alter the proteins made by those genes. Conditions caused by a change in the number or structure of chromosomes are known as chromosomal disorders. Human cells normally contain 23 pairs of chromosomes, for a total of 46 chromosomes in each cell. A change in the number of chromosomes leads to a chromosomal disorder. These

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changes can occur during the formation of reproductive cells (eggs and sperm) or in early fetal development. A gain or loss of chromosomes from the normal 46 is called aneuploidy. The most common form of aneuploidy is trisomy, or the presence of an extra chromosome in each cell. “Tri-” is Greek for “three”; people with trisomy have three copies of a particular chromosome in each cell instead of the normal two copies. Down syndrome is an example of a condition caused by trisomy—people with Down syndrome typically have three copies of chromosome 21 in each cell, for a total of 47 chromosomes per cell. Monosomy, or the loss of one chromosome from each cell, is another kind of aneuploidy. “Mono-” is Greek for “one”; people with monosomy have one copy of a particular chromosome in each cell instead of the normal two copies. Turner syndrome is a condition caused by monosomy. Women with Turner syndrome are often missing one copy of the X chromosome in every cell, for a total of 45 chromosomes per cell. Chromosomal disorders can also be caused by changes in chromosome structure. These changes are caused by the breakage and reunion of chromosome segments when an egg or sperm cell is formed or in early fetal development. Pieces of DNA can be rearranged within one chromosome, or transferred between two or more chromosomes. The effects of structural changes depend on their size and location. Many different structural changes are possible; some cause medical problems, while others may have no effect on a person’s health. Many cancer cells also have changes in their chromosome number or structure. These changes most often occur in somatic cells (cells other than eggs and sperm) during a person’s lifetime. Can Changes in Mitochondrial DNA Affect Health and Development? Mitochondria are structures within cells that convert the energy from food into a form that cells can use. Although most DNA is packaged in chromosomes within the nucleus, mitochondria also have a small amount of their own DNA (known as mitochondrial DNA or mtDNA). In some cases, inherited changes in mitochondrial DNA can cause problems with growth, development, and function of the body’s systems. These mutations disrupt the mitochondria’s ability to generate energy efficiently for the cell. Conditions caused by mutations in mitochondrial DNA often involve multiple organ systems. The effects of these conditions are most pronounced in organs and tissues that require a lot of energy (such as the heart, brain, and muscles). Although the health consequences of inherited mitochondrial DNA mutations vary widely, frequently observed features include muscle weakness and wasting, problems with movement, diabetes, kidney failure, heart disease, loss of intellectual functions (dementia), hearing loss, and abnormalities involving the eyes and vision. Mitochondrial DNA is also prone to noninherited (somatic) mutations. Somatic mutations occur in the DNA of certain cells during a person’s lifetime, and typically are not passed to future generations. Because mitochondrial DNA has a limited ability to repair itself when it is damaged, these mutations tend to build up over time. A buildup of somatic mutations in mitochondrial DNA has been associated with some forms of cancer and an increased risk of certain age-related disorders such as heart disease, Alzheimer disease, and Parkinson disease. Additionally, research suggests that the progressive accumulation of these mutations over a person’s lifetime may play a role in the normal process of aging.

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What Are Complex or Multifactorial Disorders? Researchers are learning that nearly all conditions and diseases have a genetic component. Some disorders, such as sickle cell anemia and cystic fibrosis, are caused by mutations in a single gene. The causes of many other disorders, however, are much more complex. Common medical problems such as heart disease, diabetes, and obesity do not have a single genetic cause—they are likely associated with the effects of multiple genes in combination with lifestyle and environmental factors. Conditions caused by many contributing factors are called complex or multifactorial disorders. Although complex disorders often cluster in families, they do not have a clear-cut pattern of inheritance. This makes it difficult to determine a person’s risk of inheriting or passing on these disorders. Complex disorders are also difficult to study and treat because the specific factors that cause most of these disorders have not yet been identified. By 2010, however, researchers predict they will have found the major contributing genes for many common complex disorders. What Information about a Genetic Condition Can Statistics Provide? Statistical data can provide general information about how common a condition is, how many people have the condition, or how likely it is that a person will develop the condition. Statistics are not personalized, however—they offer estimates based on groups of people. By taking into account a person’s family history, medical history, and other factors, a genetics professional can help interpret what statistics mean for a particular patient. Common Statistical Terms Some statistical terms are commonly used when describing genetic conditions and other disorders. These terms include: Statistical Term Incidence

Description The incidence of a gene mutation or a genetic disorder is the number of people who are born with the mutation or disorder in a specified group per year. Incidence is often written in the form “1 in [a number]” or as a total number of live births.

Examples About 1 in 200,000 people in the United States are born with syndrome A each year. An estimated 15,000 infants with syndrome B were born last year worldwide.

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Prevalence

The prevalence of a gene mutation or a genetic disorder is the total number of people in a specified group at a given time who have the mutation or disorder. This term includes both newly diagnosed and preexisting cases in people of any age. Prevalence is often written in the form “1 in [a number]” or as a total number of people who have a condition.

Approximately 1 in 100,000 people in the United States have syndrome A at the present time. About 100,000 children worldwide currently have syndrome B.

Mortality

Mortality is the number of deaths from a particular disorder occurring in a specified group per year. Mortality is usually expressed as a total number of deaths.

An estimated 12,000 people worldwide died from syndrome C in 2002.

Lifetime risk

Lifetime risk is the average risk of developing a particular disorder at some point during a lifetime. Lifetime risk is often written as a percentage or as “1 in [a number].” It is important to remember that the risk per year or per decade is much lower than the lifetime risk. In addition, other factors may increase or decrease a person’s risk as compared with the average.

Approximately 1 percent of people in the United States develop disorder D during their lifetimes. The lifetime risk of developing disorder D is 1 in 100.

Naming Genetic Conditions Genetic conditions are not named in one standard way (unlike genes, which are given an official name and symbol by a formal committee). Doctors who treat families with a particular disorder are often the first to propose a name for the condition. Expert working groups may later revise the name to improve its usefulness. Naming is important because it allows accurate and effective communication about particular conditions, which will ultimately help researchers find new approaches to treatment. Disorder names are often derived from one or a combination of sources: •

The basic genetic or biochemical defect that causes the condition (for example, alpha-1 antitrypsin deficiency)

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One or more major signs or symptoms of the disorder (for example, sickle cell anemia)

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The parts of the body affected by the condition (for example, retinoblastoma)

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The name of a physician or researcher, often the first person to describe the disorder (for example, Marfan syndrome, which was named after Dr. Antoine Bernard-Jean Marfan)

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A geographic area (for example, familial Mediterranean fever, which occurs mainly in populations bordering the Mediterranean Sea)

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The name of a patient or family with the condition (for example, amyotrophic lateral sclerosis, which is also called Lou Gehrig disease after a famous baseball player who had the condition).

Disorders named after a specific person or place are called eponyms. There is debate as to whether the possessive form (e.g., Alzheimer’s disease) or the nonpossessive form (Alzheimer disease) of eponyms is preferred. As a rule, medical geneticists use the nonpossessive form, and this form may become the standard for doctors in all fields of medicine. Genetics Home Reference uses the nonpossessive form of eponyms. Genetics Home Reference consults with experts in the field of medical genetics to provide the current, most accurate name for each disorder. Alternate names are included as synonyms. Naming genes The HUGO Gene Nomenclature Committee (HGNC) designates an official name and symbol (an abbreviation of the name) for each known human gene. Some official gene names include additional information in parentheses, such as related genetic conditions, subtypes of a condition, or inheritance pattern. The HGNC is a non-profit organization funded by the U.K. Medical Research Council and the U.S. National Institutes of Health. The Committee has named more than 13,000 of the estimated 20,000 to 25,000 genes in the human genome. During the research process, genes often acquire several alternate names and symbols. Different researchers investigating the same gene may each give the gene a different name, which can cause confusion. The HGNC assigns a unique name and symbol to each human gene, which allows effective organization of genes in large databanks, aiding the advancement of research. For specific information about how genes are named, refer to the HGNC’s Guidelines for Human Gene Nomenclature. Genetics Home Reference describes genes using the HGNC’s official gene names and gene symbols. Genetics Home Reference frequently presents the symbol and name separated with a colon (for example, FGFR4: Fibroblast growth factor receptor 4).

Inheriting Genetic Conditions This section gives you information on inheritance patterns and understanding risk. What Does It Mean If a Disorder Seems to Run in My Family? A particular disorder might be described as “running in a family” if more than one person in the family has the condition. Some disorders that affect multiple family members are caused by gene mutations, which can be inherited (passed down from parent to child). Other conditions that appear to run in families are not inherited. Instead, environmental factors such as dietary habits or a combination of genetic and environmental factors are responsible for these disorders.

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It is not always easy to determine whether a condition in a family is inherited. A genetics professional can use a person’s family history (a record of health information about a person’s immediate and extended family) to help determine whether a disorder has a genetic component.

Some disorders are seen in more than one generation of a family. Why Is It Important to Know My Family Medical History? A family medical history is a record of health information about a person and his or her close relatives. A complete record includes information from three generations of relatives, including children, brothers and sisters, parents, aunts and uncles, nieces and nephews, grandparents, and cousins.

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Families have many factors in common, including their genes, environment, and lifestyle. Together, these factors can give clues to medical conditions that may run in a family. By noticing patterns of disorders among relatives, healthcare professionals can determine whether an individual, other family members, or future generations may be at an increased risk of developing a particular condition. A family medical history can identify people with a higher-than-usual chance of having common disorders, such as heart disease, high blood pressure, stroke, certain cancers, and diabetes. These complex disorders are influenced by a combination of genetic factors, environmental conditions, and lifestyle choices. A family history also can provide information about the risk of rarer conditions caused by mutations in a single gene, such as cystic fibrosis and sickle cell anemia. While a family medical history provides information about the risk of specific health concerns, having relatives with a medical condition does not mean that an individual will definitely develop that condition. On the other hand, a person with no family history of a disorder may still be at risk of developing that disorder. Knowing one’s family medical history allows a person to take steps to reduce his or her risk. For people at an increased risk of certain cancers, healthcare professionals may recommend more frequent screening (such as mammography or colonoscopy) starting at an earlier age. Healthcare providers may also encourage regular checkups or testing for people with a medical condition that runs in their family. Additionally, lifestyle changes such as adopting a healthier diet, getting regular exercise, and quitting smoking help many people lower their chances of developing heart disease and other common illnesses. The easiest way to get information about family medical history is to talk to relatives about their health. Have they had any medical problems, and when did they occur? A family gathering could be a good time to discuss these issues. Additionally, obtaining medical records and other documents (such as obituaries and death certificates) can help complete a family medical history. It is important to keep this information up-to-date and to share it with a healthcare professional regularly. What Are the Different Ways in which a Genetic Condition Can Be Inherited? Some genetic conditions are caused by mutations in a single gene. These conditions are usually inherited in one of several straightforward patterns, depending on the gene involved: Inheritance Pattern Autosomal dominant

Description One mutated copy of the gene in each cell is sufficient for a person to be affected by an autosomal dominant disorder. Each affected person usually has one affected parent. Autosomal dominant disorders tend to occur in every generation of an affected family.

Examples Huntington disease, neurofibromatosis type 1

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Autosomal recessive

Two mutated copies of the gene are present in each cell when a person has an autosomal recessive disorder. An affected person usually has unaffected parents who each carry a single copy of the mutated gene (and are referred to as carriers). Autosomal recessive disorders are typically not seen in every generation of an affected family.

cystic fibrosis, sickle cell anemia

X-linked dominant

X-linked dominant disorders are caused by mutations in genes on the X chromosome. Females are more frequently affected than males, and the chance of passing on an X-linked dominant disorder differs between men and women. Families with an X-linked dominant disorder often have both affected males and affected females in each generation. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons (no male-to-male transmission).

fragile X syndrome

X-linked recessive

X-linked recessive disorders are also caused by mutations in genes on the X chromosome. Males are more frequently affected than females, and the chance of passing on the disorder differs between men and women. Families with an X-linked recessive disorder often have affected males, but rarely affected females, in each generation. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons (no male-to-male transmission).

hemophilia, Fabry disease

Codominant

In codominant inheritance, two different versions (alleles) of a gene can be expressed, and each version makes a slightly different protein. Both alleles influence the genetic trait or determine the characteristics of the genetic condition.

ABO blood group, alpha-1 antitrypsin deficiency

Mitochondrial

This type of inheritance, also known as maternal inheritance, applies to genes in mitochondrial DNA. Mitochondria, which are structures in each cell that convert molecules into energy, each contain a small amount of DNA. Because only egg cells contribute mitochondria to the developing embryo, only females can pass on mitochondrial conditions to their children. Mitochondrial disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass mitochondrial traits to their children.

Leber hereditary optic neuropathy (LHON)

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Many other disorders are caused by a combination of the effects of multiple genes or by interactions between genes and the environment. Such disorders are more difficult to analyze because their genetic causes are often unclear, and they do not follow the patterns of inheritance described above. Examples of conditions caused by multiple genes or gene/environment interactions include heart disease, diabetes, schizophrenia, and certain types of cancer. Disorders caused by changes in the number or structure of chromosomes do not follow the straightforward patterns of inheritance listed above. Other genetic factors can also influence how a disorder is inherited. If a Genetic Disorder Runs in My Family, What Are the Chances That My Children Will Have the Condition? When a genetic disorder is diagnosed in a family, family members often want to know the likelihood that they or their children will develop the condition. This can be difficult to predict in some cases because many factors influence a person’s chances of developing a genetic condition. One important factor is how the condition is inherited. For example: •

Autosomal dominant inheritance: A person affected by an autosomal dominant disorder has a 50 percent chance of passing the mutated gene to each child. The chance that a child will not inherit the mutated gene is also 50 percent.

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Autosomal recessive inheritance: Two unaffected people who each carry one copy of the mutated gene for an autosomal recessive disorder (carriers) have a 25 percent chance with each pregnancy of having a child affected by the disorder. The chance with each pregnancy of having an unaffected child who is a carrier of the disorder is 50 percent, and the chance that a child will not have the disorder and will not be a carrier is 25 percent.

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X-linked dominant inheritance: The chance of passing on an X-linked dominant condition differs between men and women because men have one X chromosome and one Y chromosome, while women have two X chromosomes. A man passes on his Y chromosome to all of his sons and his X chromosome to all of his daughters. Therefore, the sons of a man with an X-linked dominant disorder will not be affected, but all of his daughters will inherit the condition. A woman passes on one or the other of her X chromosomes to each child. Therefore, a woman with an X-linked dominant disorder has a 50 percent chance of having an affected daughter or son with each pregnancy.

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X-linked recessive inheritance: Because of the difference in sex chromosomes, the probability of passing on an X-linked recessive disorder also differs between men and women. The sons of a man with an X-linked recessive disorder will not be affected, and his daughters will carry one copy of the mutated gene. With each pregnancy, a woman who carries an X-linked recessive disorder has a 50 percent chance of having sons who are affected and a 50 percent chance of having daughters who carry one copy of the mutated gene.

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Codominant inheritance: In codominant inheritance, each parent contributes a different version of a particular gene, and both versions influence the resulting genetic trait. The chance of developing a genetic condition with codominant inheritance, and the characteristic features of that condition, depend on which versions of the gene are passed from parents to their child.

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Mitochondrial inheritance: Mitochondria, which are the energy-producing centers inside cells, each contain a small amount of DNA. Disorders with mitochondrial inheritance result from mutations in mitochondrial DNA. Although mitochondrial

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disorders can affect both males and females, only females can pass mutations in mitochondrial DNA to their children. A woman with a disorder caused by changes in mitochondrial DNA will pass the mutation to all of her daughters and sons, but the children of a man with such a disorder will not inherit the mutation. It is important to note that the chance of passing on a genetic condition applies equally to each pregnancy. For example, if a couple has a child with an autosomal recessive disorder, the chance of having another child with the disorder is still 25 percent (or 1 in 4). Having one child with a disorder does not “protect” future children from inheriting the condition. Conversely, having a child without the condition does not mean that future children will definitely be affected. Although the chances of inheriting a genetic condition appear straightforward, factors such as a person’s family history and the results of genetic testing can sometimes modify those chances. In addition, some people with a disease-causing mutation never develop any health problems or may experience only mild symptoms of the disorder. If a disease that runs in a family does not have a clear-cut inheritance pattern, predicting the likelihood that a person will develop the condition can be particularly difficult. Estimating the chance of developing or passing on a genetic disorder can be complex. Genetics professionals can help people understand these chances and help them make informed decisions about their health. Factors that Influence the Effects of Particular Genetic Changes Reduced penetrance and variable expressivity are factors that influence the effects of particular genetic changes. These factors usually affect disorders that have an autosomal dominant pattern of inheritance, although they are occasionally seen in disorders with an autosomal recessive inheritance pattern. Reduced Penetrance Penetrance refers to the proportion of people with a particular genetic change (such as a mutation in a specific gene) who exhibit signs and symptoms of a genetic disorder. If some people with the mutation do not develop features of the disorder, the condition is said to have reduced (or incomplete) penetrance. Reduced penetrance often occurs with familial cancer syndromes. For example, many people with a mutation in the BRCA1 or BRCA2 gene will develop cancer during their lifetime, but some people will not. Doctors cannot predict which people with these mutations will develop cancer or when the tumors will develop. Reduced penetrance probably results from a combination of genetic, environmental, and lifestyle factors, many of which are unknown. This phenomenon can make it challenging for genetics professionals to interpret a person’s family medical history and predict the risk of passing a genetic condition to future generations. Variable Expressivity Although some genetic disorders exhibit little variation, most have signs and symptoms that differ among affected individuals. Variable expressivity refers to the range of signs and

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symptoms that can occur in different people with the same genetic condition. For example, the features of Marfan syndrome vary widely— some people have only mild symptoms (such as being tall and thin with long, slender fingers), while others also experience lifethreatening complications involving the heart and blood vessels. Although the features are highly variable, most people with this disorder have a mutation in the same gene (FBN1). As with reduced penetrance, variable expressivity is probably caused by a combination of genetic, environmental, and lifestyle factors, most of which have not been identified. If a genetic condition has highly variable signs and symptoms, it may be challenging to diagnose. What Do Geneticists Mean by Anticipation? The signs and symptoms of some genetic conditions tend to become more severe and appear at an earlier age as the disorder is passed from one generation to the next. This phenomenon is called anticipation. Anticipation is most often seen with certain genetic disorders of the nervous system, such as Huntington disease, myotonic dystrophy, and fragile X syndrome. Anticipation typically occurs with disorders that are caused by an unusual type of mutation called a trinucleotide repeat expansion. A trinucleotide repeat is a sequence of three DNA building blocks (nucleotides) that is repeated a number of times in a row. DNA segments with an abnormal number of these repeats are unstable and prone to errors during cell division. The number of repeats can change as the gene is passed from parent to child. If the number of repeats increases, it is known as a trinucleotide repeat expansion. In some cases, the trinucleotide repeat may expand until the gene stops functioning normally. This expansion causes the features of some disorders to become more severe with each successive generation. Most genetic disorders have signs and symptoms that differ among affected individuals, including affected people in the same family. Not all of these differences can be explained by anticipation. A combination of genetic, environmental, and lifestyle factors is probably responsible for the variability, although many of these factors have not been identified. Researchers study multiple generations of affected family members and consider the genetic cause of a disorder before determining that it shows anticipation. What Is Genomic Imprinting? Genomic imprinting is a factor that influences how some genetic conditions are inherited. People inherit two copies of their genes—one from their mother and one from their father. Usually both copies of each gene are active, or “turned on,” in cells. In some cases, however, only one of the two copies is normally turned on. Which copy is active depends on the parent of origin: some genes are normally active only when they are inherited from a person’s father; others are active only when inherited from a person’s mother. This phenomenon is known as genomic imprinting. In genes that undergo genomic imprinting, the parent of origin is often marked, or “stamped,” on the gene during the formation of egg and sperm cells. This stamping process, called methylation, is a chemical reaction that attaches small molecules called methyl groups to certain segments of DNA. These molecules identify which copy of a gene was inherited

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from the mother and which was inherited from the father. The addition and removal of methyl groups can be used to control the activity of genes. Only a small percentage of all human genes undergo genomic imprinting. Researchers are not yet certain why some genes are imprinted and others are not. They do know that imprinted genes tend to cluster together in the same regions of chromosomes. Two major clusters of imprinted genes have been identified in humans, one on the short (p) arm of chromosome 11 (at position 11p15) and another on the long (q) arm of chromosome 15 (in the region 15q11 to 15q13). What Is Uniparental Disomy? Uniparental disomy is a factor that influences how some genetic conditions are inherited. Uniparental disomy (UPD) occurs when a person receives two copies of a chromosome, or part of a chromosome, from one parent and no copies from the other parent. UPD can occur as a random event during the formation of egg or sperm cells or may happen in early fetal development. In many cases, UPD likely has no effect on health or development. Because most genes are not imprinted, it doesn’t matter if a person inherits both copies from one parent instead of one copy from each parent. In some cases, however, it does make a difference whether a gene is inherited from a person’s mother or father. A person with UPD may lack any active copies of essential genes that undergo genomic imprinting. This loss of gene function can lead to delayed development, mental retardation, or other medical problems. Several genetic disorders can result from UPD or a disruption of normal genomic imprinting. The most well-known conditions include Prader-Willi syndrome, which is characterized by uncontrolled eating and obesity, and Angelman syndrome, which causes mental retardation and impaired speech. Both of these disorders can be caused by UPD or other errors in imprinting involving genes on the long arm of chromosome 15. Other conditions, such as Beckwith-Wiedemann syndrome (a disorder characterized by accelerated growth and an increased risk of cancerous tumors), are associated with abnormalities of imprinted genes on the short arm of chromosome 11. Are Chromosomal Disorders Inherited? Although it is possible to inherit some types of chromosomal abnormalities, most chromosomal disorders (such as Down syndrome and Turner syndrome) are not passed from one generation to the next. Some chromosomal conditions are caused by changes in the number of chromosomes. These changes are not inherited, but occur as random events during the formation of reproductive cells (eggs and sperm). An error in cell division called nondisjunction results in reproductive cells with an abnormal number of chromosomes. For example, a reproductive cell may accidentally gain or lose one copy of a chromosome. If one of these atypical reproductive cells contributes to the genetic makeup of a child, the child will have an extra or missing chromosome in each of the body’s cells.

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Changes in chromosome structure can also cause chromosomal disorders. Some changes in chromosome structure can be inherited, while others occur as random accidents during the formation of reproductive cells or in early fetal development. Because the inheritance of these changes can be complex, people concerned about this type of chromosomal abnormality may want to talk with a genetics professional. Some cancer cells also have changes in the number or structure of their chromosomes. Because these changes occur in somatic cells (cells other than eggs and sperm), they cannot be passed from one generation to the next. Why Are Some Genetic Conditions More Common in Particular Ethnic Groups? Some genetic disorders are more likely to occur among people who trace their ancestry to a particular geographic area. People in an ethnic group often share certain versions of their genes, which have been passed down from common ancestors. If one of these shared genes contains a disease-causing mutation, a particular genetic disorder may be more frequently seen in the group. Examples of genetic conditions that are more common in particular ethnic groups are sickle cell anemia, which is more common in people of African, African-American, or Mediterranean heritage; and Tay-Sachs disease, which is more likely to occur among people of Ashkenazi (eastern and central European) Jewish or French Canadian ancestry. It is important to note, however, that these disorders can occur in any ethnic group.

Genetic Consultation This section presents information on finding and visiting a genetic counselor or other genetics professional. What Is a Genetic Consultation? A genetic consultation is a health service that provides information and support to people who have, or may be at risk for, genetic disorders. During a consultation, a genetics professional meets with an individual or family to discuss genetic risks or to diagnose, confirm, or rule out a genetic condition. Genetics professionals include medical geneticists (doctors who specialize in genetics) and genetic counselors (certified healthcare workers with experience in medical genetics and counseling). Other healthcare professionals such as nurses, psychologists, and social workers trained in genetics can also provide genetic consultations. Consultations usually take place in a doctor’s office, hospital, genetics center, or other type of medical center. These meetings are most often in-person visits with individuals or families, but they are occasionally conducted in a group or over the telephone.

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Why Might Someone Have a Genetic Consultation? Individuals or families who are concerned about an inherited condition may benefit from a genetic consultation. The reasons that a person might be referred to a genetic counselor, medical geneticist, or other genetics professional include: •

A personal or family history of a genetic condition, birth defect, chromosomal disorder, or hereditary cancer.

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Two or more pregnancy losses (miscarriages), a stillbirth, or a baby who died.

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A child with a known inherited disorder, a birth defect, mental retardation, or developmental delay.

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A woman who is pregnant or plans to become pregnant at or after age 35. (Some chromosomal disorders occur more frequently in children born to older women.)

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Abnormal test results that suggest a genetic or chromosomal condition.

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An increased risk of developing or passing on a particular genetic disorder on the basis of a person’s ethnic background.

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People related by blood (for example, cousins) who plan to have children together. (A child whose parents are related may be at an increased risk of inheriting certain genetic disorders.)

A genetic consultation is also an important part of the decision-making process for genetic testing. A visit with a genetics professional may be helpful even if testing is not available for a specific condition, however. What Happens during a Genetic Consultation? A genetic consultation provides information, offers support, and addresses a patient’s specific questions and concerns. To help determine whether a condition has a genetic component, a genetics professional asks about a person’s medical history and takes a detailed family history (a record of health information about a person’s immediate and extended family). The genetics professional may also perform a physical examination and recommend appropriate tests. If a person is diagnosed with a genetic condition, the genetics professional provides information about the diagnosis, how the condition is inherited, the chance of passing the condition to future generations, and the options for testing and treatment. During a consultation, a genetics professional will: •

Interpret and communicate complex medical information.

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Help each person make informed, independent decisions about their health care and reproductive options.

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Respect each person’s individual beliefs, traditions, and feelings.

A genetics professional will NOT: •

Tell a person which decision to make.

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Advise a couple not to have children.

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Recommend that a woman continue or end a pregnancy.

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Tell someone whether to undergo testing for a genetic disorder.

How Can I Find a Genetics Professional in My Area? To find a genetics professional in your community, you may wish to ask your doctor for a referral. If you have health insurance, you can also contact your insurance company to find a medical geneticist or genetic counselor in your area who participates in your plan. Several resources for locating a genetics professional in your community are available online: •

GeneTests from the University of Washington provides a list of genetics clinics around the United States and international genetics clinics. You can also access the list by clicking on “Clinic Directory” at the top of the GeneTests home page. Clinics can be chosen by state or country, by service, and/or by specialty. State maps can help you locate a clinic in your area. See http://www.genetests.org/.

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The National Society of Genetic Counselors offers a searchable directory of genetic counselors in the United States. You can search by location, name, area of practice/specialization, and/or ZIP Code. See http://www.nsgc.org/resourcelink.cfm.

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The National Cancer Institute provides a Cancer Genetics Services Directory, which lists professionals who provide services related to cancer genetics. You can search by type of cancer or syndrome, location, and/or provider name at the following Web site: http://cancer.gov/search/genetics_services/.

Genetic Testing This section presents information on the benefits, costs, risks, and limitations of genetic testing. What Is Genetic Testing? Genetic testing is a type of medical test that identifies changes in chromosomes, genes, or proteins. Most of the time, testing is used to find changes that are associated with inherited disorders. The results of a genetic test can confirm or rule out a suspected genetic condition or help determine a person’s chance of developing or passing on a genetic disorder. Several hundred genetic tests are currently in use, and more are being developed. Genetic testing is voluntary. Because testing has both benefits and limitations, the decision about whether to be tested is a personal and complex one. A genetic counselor can help by providing information about the pros and cons of the test and discussing the social and emotional aspects of testing.

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What Are the Types of Genetic Tests? Genetic testing can provide information about a person’s genes and chromosomes. Available types of testing include: •

Newborn screening is used just after birth to identify genetic disorders that can be treated early in life. Millions of babies are tested each year in the United States. All states currently test infants for phenylketonuria (a genetic disorder that causes mental retardation if left untreated) and congenital hypothyroidism (a disorder of the thyroid gland). Most states also test for other genetic disorders.

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Diagnostic testing is used to identify or rule out a specific genetic or chromosomal condition. In many cases, genetic testing is used to confirm a diagnosis when a particular condition is suspected based on physical signs and symptoms. Diagnostic testing can be performed before birth or at any time during a person’s life, but is not available for all genes or all genetic conditions. The results of a diagnostic test can influence a person’s choices about health care and the management of the disorder.

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Carrier testing is used to identify people who carry one copy of a gene mutation that, when present in two copies, causes a genetic disorder. This type of testing is offered to individuals who have a family history of a genetic disorder and to people in certain ethnic groups with an increased risk of specific genetic conditions. If both parents are tested, the test can provide information about a couple’s risk of having a child with a genetic condition.

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Prenatal testing is used to detect changes in a fetus’s genes or chromosomes before birth. This type of testing is offered during pregnancy if there is an increased risk that the baby will have a genetic or chromosomal disorder. In some cases, prenatal testing can lessen a couple’s uncertainty or help them make decisions about a pregnancy. It cannot identify all possible inherited disorders and birth defects, however.

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Preimplantation testing, also called preimplantation genetic diagnosis (PGD), is a specialized technique that can reduce the risk of having a child with a particular genetic or chromosomal disorder. It is used to detect genetic changes in embryos that were created using assisted reproductive techniques such as in-vitro fertilization. In-vitro fertilization involves removing egg cells from a woman’s ovaries and fertilizing them with sperm cells outside the body. To perform preimplantation testing, a small number of cells are taken from these embryos and tested for certain genetic changes. Only embryos without these changes are implanted in the uterus to initiate a pregnancy.

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Predictive and presymptomatic types of testing are used to detect gene mutations associated with disorders that appear after birth, often later in life. These tests can be helpful to people who have a family member with a genetic disorder, but who have no features of the disorder themselves at the time of testing. Predictive testing can identify mutations that increase a person’s risk of developing disorders with a genetic basis, such as certain types of cancer. Presymptomatic testing can determine whether a person will develop a genetic disorder, such as hemochromatosis (an iron overload disorder), before any signs or symptoms appear. The results of predictive and presymptomatic testing can provide information about a person’s risk of developing a specific disorder and help with making decisions about medical care.

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Forensic testing uses DNA sequences to identify an individual for legal purposes. Unlike the tests described above, forensic testing is not used to detect gene mutations associated with disease. This type of testing can identify crime or catastrophe victims, rule out or implicate a crime suspect, or establish biological relationships between people (for example, paternity).

Help Me Understand Genetics

How Is Genetic Testing Done? Once a person decides to proceed with genetic testing, a medical geneticist, primary care doctor, specialist, or nurse practitioner can order the test. Genetic testing is often done as part of a genetic consultation. Genetic tests are performed on a sample of blood, hair, skin, amniotic fluid (the fluid that surrounds a fetus during pregnancy), or other tissue. For example, a procedure called a buccal smear uses a small brush or cotton swab to collect a sample of cells from the inside surface of the cheek. The sample is sent to a laboratory where technicians look for specific changes in chromosomes, DNA, or proteins, depending on the suspected disorder. The laboratory reports the test results in writing to a person’s doctor or genetic counselor. Newborn screening tests are done on a small blood sample, which is taken by pricking the baby’s heel. Unlike other types of genetic testing, a parent will usually only receive the result if it is positive. If the test result is positive, additional testing is needed to determine whether the baby has a genetic disorder. Before a person has a genetic test, it is important that he or she understands the testing procedure, the benefits and limitations of the test, and the possible consequences of the test results. The process of educating a person about the test and obtaining permission is called informed consent. What Is Direct-to-Consumer Genetic Testing? Traditionally, genetic tests have been available only through healthcare providers such as physicians, nurse practitioners, and genetic counselors. Healthcare providers order the appropriate test from a laboratory, collect and send the samples, and interpret the test results. Direct-to-consumer genetic testing refers to genetic tests that are marketed directly to consumers via television, print advertisem*nts, or the Internet. This form of testing, which is also known as at-home genetic testing, provides access to a person’s genetic information without necessarily involving a doctor or insurance company in the process. If a consumer chooses to purchase a genetic test directly, the test kit is mailed to the consumer instead of being ordered through a doctor’s office. The test typically involves collecting a DNA sample at home, often by swabbing the inside of the cheek, and mailing the sample back to the laboratory. In some cases, the person must visit a health clinic to have blood drawn. Consumers are notified of their results by mail or over the telephone, or the results are posted online. In some cases, a genetic counselor or other healthcare provider is available to explain the results and answer questions. The price for this type of at-home genetic testing ranges from several hundred dollars to more than a thousand dollars. The growing market for direct-to-consumer genetic testing may promote awareness of genetic diseases, allow consumers to take a more proactive role in their health care, and offer a means for people to learn about their ancestral origins. At-home genetic tests, however, have significant risks and limitations. Consumers are vulnerable to being misled by the results of unproven or invalid tests. Without guidance from a healthcare provider, they may make important decisions about treatment or prevention based on inaccurate, incomplete, or misunderstood information about their health. Consumers may also experience an invasion

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of genetic privacy if testing companies use their genetic information in an unauthorized way. Genetic testing provides only one piece of information about a person’s health—other genetic and environmental factors, lifestyle choices, and family medical history also affect a person’s risk of developing many disorders. These factors are discussed during a consultation with a doctor or genetic counselor, but in many cases are not addressed by athome genetic tests. More research is needed to fully understand the benefits and limitations of direct-to-consumer genetic testing. What Do the Results of Genetic Tests Mean? The results of genetic tests are not always straightforward, which often makes them challenging to interpret and explain. Therefore, it is important for patients and their families to ask questions about the potential meaning of genetic test results both before and after the test is performed. When interpreting test results, healthcare professionals consider a person’s medical history, family history, and the type of genetic test that was done. A positive test result means that the laboratory found a change in a particular gene, chromosome, or protein of interest. Depending on the purpose of the test, this result may confirm a diagnosis, indicate that a person is a carrier of a particular genetic mutation, identify an increased risk of developing a disease (such as cancer) in the future, or suggest a need for further testing. Because family members have some genetic material in common, a positive test result may also have implications for certain blood relatives of the person undergoing testing. It is important to note that a positive result of a predictive or presymptomatic genetic test usually cannot establish the exact risk of developing a disorder. Also, health professionals typically cannot use a positive test result to predict the course or severity of a condition. A negative test result means that the laboratory did not find a change in the gene, chromosome, or protein under consideration. This result can indicate that a person is not affected by a particular disorder, is not a carrier of a specific genetic mutation, or does not have an increased risk of developing a certain disease. It is possible, however, that the test missed a disease-causing genetic alteration because many tests cannot detect all genetic changes that can cause a particular disorder. Further testing may be required to confirm a negative result. In some cases, a negative result might not give any useful information. This type of result is called uninformative, indeterminate, inconclusive, or ambiguous. Uninformative test results sometimes occur because everyone has common, natural variations in their DNA, called polymorphisms, that do not affect health. If a genetic test finds a change in DNA that has not been associated with a disorder in other people, it can be difficult to tell whether it is a natural polymorphism or a disease-causing mutation. An uninformative result cannot confirm or rule out a specific diagnosis, and it cannot indicate whether a person has an increased risk of developing a disorder. In some cases, testing other affected and unaffected family members can help clarify this type of result.

Help Me Understand Genetics

What Is the Cost of Genetic Testing, and How Long Does It Take to Get the Results? The cost of genetic testing can range from under $100 to more than $2,000, depending on the nature and complexity of the test. The cost increases if more than one test is necessary or if multiple family members must be tested to obtain a meaningful result. For newborn screening, costs vary by state. Some states cover part of the total cost, but most charge a fee of $15 to $60 per infant. From the date that a sample is taken, it may take a few weeks to several months to receive the test results. Results for prenatal testing are usually available more quickly because time is an important consideration in making decisions about a pregnancy. The doctor or genetic counselor who orders a particular test can provide specific information about the cost and time frame associated with that test. Will Health Insurance Cover the Costs of Genetic Testing? In many cases, health insurance plans will cover the costs of genetic testing when it is recommended by a person’s doctor. Health insurance providers have different policies about which tests are covered, however. A person interested in submitting the costs of testing may wish to contact his or her insurance company beforehand to ask about coverage. Some people may choose not to use their insurance to pay for testing because the results of a genetic test can affect a person’s health insurance coverage. Instead, they may opt to pay out-of-pocket for the test. People considering genetic testing may want to find out more about their state’s privacy protection laws before they ask their insurance company to cover the costs. What Are the Benefits of Genetic Testing? Genetic testing has potential benefits whether the results are positive or negative for a gene mutation. Test results can provide a sense of relief from uncertainty and help people make informed decisions about managing their health care. For example, a negative result can eliminate the need for unnecessary checkups and screening tests in some cases. A positive result can direct a person toward available prevention, monitoring, and treatment options. Some test results can also help people make decisions about having children. Newborn screening can identify genetic disorders early in life so treatment can be started as early as possible. What Are the Risks and Limitations of Genetic Testing? The physical risks associated with most genetic tests are very small, particularly for those tests that require only a blood sample or buccal smear (a procedure that samples cells from the inside surface of the cheek). The procedures used for prenatal testing carry a small but real risk of losing the pregnancy (miscarriage) because they require a sample of amniotic fluid or tissue from around the fetus. Many of the risks associated with genetic testing involve the emotional, social, or financial consequences of the test results. People may feel angry, depressed, anxious, or guilty about

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their results. In some cases, genetic testing creates tension within a family because the results can reveal information about other family members in addition to the person who is tested. The possibility of genetic discrimination in employment or insurance is also a concern. Genetic testing can provide only limited information about an inherited condition. The test often can’t determine if a person will show symptoms of a disorder, how severe the symptoms will be, or whether the disorder will progress over time. Another major limitation is the lack of treatment strategies for many genetic disorders once they are diagnosed. A genetics professional can explain in detail the benefits, risks, and limitations of a particular test. It is important that any person who is considering genetic testing understand and weigh these factors before making a decision. What Is Genetic Discrimination? Genetic discrimination occurs when people are treated differently by their employer or insurance company because they have a gene mutation that causes or increases the risk of an inherited disorder. People who undergo genetic testing may be at risk for genetic discrimination. The results of a genetic test are normally included in a person’s medical records. When a person applies for life, disability, or health insurance, the insurance company may ask to look at these records before making a decision about coverage. An employer may also have the right to look at an employee’s medical records. As a result, genetic test results could affect a person’s insurance coverage or employment. People making decisions about genetic testing should be aware that when test results are placed in their medical records, the results might not be kept private. Fear of discrimination is a common concern among people considering genetic testing. Several laws at the federal and state levels help protect people against genetic discrimination; however, genetic testing is a fast-growing field and these laws don’t cover every situation. How Does Genetic Testing in a Research Setting Differ from Clinical Genetic Testing? The main differences between clinical genetic testing and research testing are the purpose of the test and who receives the results. The goals of research testing include finding unknown genes, learning how genes work, and advancing our understanding of genetic conditions. The results of testing done as part of a research study are usually not available to patients or their healthcare providers. Clinical testing, on the other hand, is done to find out about an inherited disorder in an individual patient or family. People receive the results of a clinical test and can use them to help them make decisions about medical care or reproductive issues. It is important for people considering genetic testing to know whether the test is available on a clinical or research basis. Clinical and research testing both involve a process of informed consent in which patients learn about the testing procedure, the risks and benefits of the test, and the potential consequences of testing.

Help Me Understand Genetics

Gene Therapy This section presents information on experimental techniques, safety, ethics, and availability of gene therapy. What Is Gene Therapy? Gene therapy is an experimental technique that uses genes to treat or prevent disease. In the future, this technique may allow doctors to treat a disorder by inserting a gene into a patient’s cells instead of using drugs or surgery. Researchers are testing several approaches to gene therapy, including: •

Replacing a mutated gene that causes disease with a healthy copy of the gene.

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Inactivating, or “knocking out,” a mutated gene that is functioning improperly.

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Introducing a new gene into the body to help fight a disease.

Although gene therapy is a promising treatment option for a number of diseases (including inherited disorders, some types of cancer, and certain viral infections), the technique remains risky and is still under study to make sure that it will be safe and effective. Gene therapy is currently only being tested for the treatment of diseases that have no other cures. How Does Gene Therapy Work? Gene therapy is designed to introduce genetic material into cells to compensate for abnormal genes or to make a beneficial protein. If a mutated gene causes a necessary protein to be faulty or missing, gene therapy may be able to introduce a normal copy of the gene to restore the function of the protein. A gene that is inserted directly into a cell usually does not function. Instead, a carrier called a vector is genetically engineered to deliver the gene. Certain viruses are often used as vectors because they can deliver the new gene by infecting the cell. The viruses are modified so they can’t cause disease when used in people. Some types of virus, such as retroviruses, integrate their genetic material (including the new gene) into a chromosome in the human cell. Other viruses, such as adenoviruses, introduce their DNA into the nucleus of the cell, but the DNA is not integrated into a chromosome. The vector can be injected or given intravenously (by IV) directly into a specific tissue in the body, where it is taken up by individual cells. Alternately, a sample of the patient’s cells can be removed and exposed to the vector in a laboratory setting. The cells containing the vector are then returned to the patient. If the treatment is successful, the new gene delivered by the vector will make a functioning protein. Researchers must overcome many technical challenges before gene therapy will be a practical approach to treating disease. For example, scientists must find better ways to deliver genes and target them to particular cells. They must also ensure that new genes are precisely controlled by the body.

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A new gene is injected into an adenovirus vector, which is used to introduce the modified DNA into a human cell. If the treatment is successful, the new gene will make a functional protein.

Is Gene Therapy Safe? Gene therapy is under study to determine whether it could be used to treat disease. Current research is evaluating the safety of gene therapy; future studies will test whether it is an effective treatment option. Several studies have already shown that this approach can have very serious health risks, such as toxicity, inflammation, and cancer. Because the techniques are relatively new, some of the risks may be unpredictable; however, medical researchers, institutions, and regulatory agencies are working to ensure that gene therapy research is as safe as possible. Comprehensive federal laws, regulations, and guidelines help protect people who participate in research studies (called clinical trials). The U.S. Food and Drug Administration (FDA) regulates all gene therapy products in the United States and oversees research in this area. Researchers who wish to test an approach in a clinical trial must first obtain permission from the FDA. The FDA has the authority to reject or suspend clinical trials that are suspected of being unsafe for participants. The National Institutes of Health (NIH) also plays an important role in ensuring the safety of gene therapy research. NIH provides guidelines for investigators and institutions (such as universities and hospitals) to follow when conducting clinical trials with gene therapy. These guidelines state that clinical trials at institutions receiving NIH funding for this type of research must be registered with the NIH Office of Biotechnology Activities. The protocol, or plan, for each clinical trial is then reviewed by the NIH Recombinant DNA Advisory Committee (RAC) to determine whether it raises medical, ethical, or safety issues that warrant further discussion at one of the RAC’s public meetings.

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An Institutional Review Board (IRB) and an Institutional Biosafety Committee (IBC) must approve each gene therapy clinical trial before it can be carried out. An IRB is a committee of scientific and medical advisors and consumers that reviews all research within an institution. An IBC is a group that reviews and approves an institution’s potentially hazardous research studies. Multiple levels of evaluation and oversight ensure that safety concerns are a top priority in the planning and carrying out of gene therapy research. What Are the Ethical Issues surrounding Gene Therapy? Because gene therapy involves making changes to the body’s set of basic instructions, it raises many unique ethical concerns. The ethical questions surrounding gene therapy include: •

How can “good” and “bad” uses of gene therapy be distinguished?

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Who decides which traits are normal and which constitute a disability or disorder?

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Will the high costs of gene therapy make it available only to the wealthy?

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Could the widespread use of gene therapy make society less accepting of people who are different?

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Should people be allowed to use gene therapy to enhance basic human traits such as height, intelligence, or athletic ability?

Current gene therapy research has focused on treating individuals by targeting the therapy to body cells such as bone marrow or blood cells. This type of gene therapy cannot be passed on to a person’s children. Gene therapy could be targeted to egg and sperm cells (germ cells), however, which would allow the inserted gene to be passed on to future generations. This approach is known as germline gene therapy. The idea of germline gene therapy is controversial. While it could spare future generations in a family from having a particular genetic disorder, it might affect the development of a fetus in unexpected ways or have long-term side effects that are not yet known. Because people who would be affected by germline gene therapy are not yet born, they can’t choose whether to have the treatment. Because of these ethical concerns, the U.S. Government does not allow federal funds to be used for research on germline gene therapy in people. Is Gene Therapy Available to Treat My Disorder? Gene therapy is currently available only in a research setting. The U.S. Food and Drug Administration (FDA) has not yet approved any gene therapy products for sale in the United States. Hundreds of research studies (clinical trials) are under way to test gene therapy as a treatment for genetic conditions, cancer, and HIV/AIDS. If you are interested in participating in a clinical trial, talk with your doctor or a genetics professional about how to participate. You can also search for clinical trials online. ClinicalTrials.gov, a service of the National Institutes of Health, provides easy access to information on clinical trials. You can search for

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specific trials or browse by condition or trial sponsor. You may wish to refer to a list of gene therapy trials that are accepting (or will accept) patients.

The Human Genome Project and Genomic Research This section presents information on the goals, accomplishments, and next steps in understanding the human genome. What Is a Genome? A genome is an organism’s complete set of DNA, including all of its genes. Each genome contains all of the information needed to build and maintain that organism. In humans, a copy of the entire genome—more than 3 billion DNA base pairs—is contained in all cells that have a nucleus. What Was the Human Genome Project and Why Has It Been Important? The Human Genome Project was an international research effort to determine the sequence of the human genome and identify the genes that it contains. The Project was coordinated by the National Institutes of Health and the U.S. Department of Energy. Additional contributors included universities across the United States and international partners in the United Kingdom, France, Germany, Japan, and China. The Human Genome Project formally began in 1990 and was completed in 2003, 2 years ahead of its original schedule. The work of the Human Genome Project has allowed researchers to begin to understand the blueprint for building a person. As researchers learn more about the functions of genes and proteins, this knowledge will have a major impact in the fields of medicine, biotechnology, and the life sciences. What Were the Goals of the Human Genome Project? The main goals of the Human Genome Project were to provide a complete and accurate sequence of the 3 billion DNA base pairs that make up the human genome and to find all of the estimated 20,000 to 25,000 human genes. The Project also aimed to sequence the genomes of several other organisms that are important to medical research, such as the mouse and the fruit fly. In addition to sequencing DNA, the Human Genome Project sought to develop new tools to obtain and analyze the data and to make this information widely available. Also, because advances in genetics have consequences for individuals and society, the Human Genome Project committed to exploring the consequences of genomic research through its Ethical, Legal, and Social Implications (ELSI) program. What Did the Human Genome Project Accomplish? In April 2003, researchers announced that the Human Genome Project had completed a high-quality sequence of essentially the entire human genome. This sequence closed the gaps from a working draft of the genome, which was published in 2001. It also identified the

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locations of many human genes and provided information about their structure and organization. The Project made the sequence of the human genome and tools to analyze the data freely available via the Internet. In addition to the human genome, the Human Genome Project sequenced the genomes of several other organisms, including brewers’ yeast, the roundworm, and the fruit fly. In 2002, researchers announced that they had also completed a working draft of the mouse genome. By studying the similarities and differences between human genes and those of other organisms, researchers can discover the functions of particular genes and identify which genes are critical for life. The Project’s Ethical, Legal, and Social Implications (ELSI) program became the world’s largest bioethics program and a model for other ELSI programs worldwide. What Were Some of the Ethical, Legal, and Social Implications Addressed by the Human Genome Project? The Ethical, Legal, and Social Implications (ELSI) program was founded in 1990 as an integral part of the Human Genome Project. The mission of the ELSI program was to identify and address issues raised by genomic research that would affect individuals, families, and society. A percentage of the Human Genome Project budget at the National Institutes of Health and the U.S. Department of Energy was devoted to ELSI research. The ELSI program focused on the possible consequences of genomic research in four main areas: •

Privacy and fairness in the use of genetic information, including the potential for genetic discrimination in employment and insurance.

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The integration of new genetic technologies, such as genetic testing, into the practice of clinical medicine.

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Ethical issues surrounding the design and conduct of genetic research with people, including the process of informed consent.

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The education of healthcare professionals, policy makers, students, and the public about genetics and the complex issues that result from genomic research. What Are the Next Steps in Genomic Research?

Discovering the sequence of the human genome was only the first step in understanding how the instructions coded in DNA lead to a functioning human being. The next stage of genomic research will begin to derive meaningful knowledge from the DNA sequence. Research studies that build on the work of the Human Genome Project are under way worldwide. The objectives of continued genomic research include the following: •

Determine the function of genes and the elements that regulate genes throughout the genome.

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Find variations in the DNA sequence among people and determine their significance. These variations may one day provide information about a person’s disease risk and response to certain medications.

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Discover the 3-dimensional structures of proteins and identify their functions.

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Explore how DNA and proteins interact with one another and with the environment to create complex living systems.

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Develop and apply genome-based strategies for the early detection, diagnosis, and treatment of disease.

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Sequence the genomes of other organisms, such as the rat, cow, and chimpanzee, in order to compare similar genes between species.

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Develop new technologies to study genes and DNA on a large scale and store genomic data efficiently.

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Continue to explore the ethical, legal, and social issues raised by genomic research. What Is Pharmacogenomics?

Pharmacogenomics is the study of how genes affect a person’s response to drugs. This relatively new field combines pharmacology (the science of drugs) and genomics (the study of genes and their functions) to develop effective, safe medications and doses that will be tailored to a person’s genetic makeup. Many drugs that are currently available are “one size fits all,” but they don’t work the same way for everyone. It can be difficult to predict who will benefit from a medication, who will not respond at all, and who will experience negative side effects (called adverse drug reactions). Adverse drug reactions are a significant cause of hospitalizations and deaths in the United States. With the knowledge gained from the Human Genome Project, researchers are learning how inherited differences in genes affect the body’s response to medications. These genetic differences will be used to predict whether a medication will be effective for a particular person and to help prevent adverse drug reactions. The field of pharmacogenomics is still in its infancy. Its use is currently quite limited, but new approaches are under study in clinical trials. In the future, pharmacogenomics will allow the development of tailored drugs to treat a wide range of health problems, including cardiovascular disease, Alzheimer disease, cancer, HIV/AIDS, and asthma.

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APPENDIX B. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute9: •

National Institutes of Health (NIH); guidelines consolidated across agencies available at http://health.nih.gov/

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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/Publications/FactSheets.htm

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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancertopics/pdq

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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/health/

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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/HealthInformation/Publications/

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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/Publications/

These publications are typically written by one or more of the various NIH Institutes.

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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidcr.nih.gov/HealthInformation/

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/healthinformation/index.cfm

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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

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National Institute of Biomedical Imaging and Bioengineering; general information at http://www.nibib.nih.gov/HealthEdu

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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.10 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html).

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citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine11: •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/index.html

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Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

See http://www.nlm.nih.gov/databases/index.html.

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The NLM Gateway12 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.13 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type achondroplasia (or synonyms) into the search box and click Search. The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 1689 13 28 1 0 1731

HSTAT14 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.15 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.16 Simply search by achondroplasia (or synonyms) at the following Web site: http://text.nlm.nih.gov.

Coffee Break: Tutorials for Biologists17 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are 12

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 14 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 15 16

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration’s Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force’s Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations. 17 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

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used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.18 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.19 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

MD Consult: Access to electronic clinical resources, see http://www.mdconsult.com/.

•

Medical Matrix: Lists over 6000 medical Web sites and links to over 1.5 million documents with clinical content, see http://www.medmatrix.org/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 19 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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APPENDIX C. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called Fact Sheets or Guidelines. They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on achondroplasia can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources This section directs you to sources which either publish fact sheets or can help you find additional guidelines on topics related to achondroplasia. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are health topic pages which list links to available materials relevant to achondroplasia. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for achondroplasia:

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Birth Defects http://www.nlm.nih.gov/medlineplus/birthdefects.html Bone Diseases http://www.nlm.nih.gov/medlineplus/bonediseases.html Connective Tissue Disorders http://www.nlm.nih.gov/medlineplus/connectivetissuedisorders.html Dwarfism http://www.nlm.nih.gov/medlineplus/dwarfism.html Genetic Disorders http://www.nlm.nih.gov/medlineplus/geneticdisorders.html Growth Disorders http://www.nlm.nih.gov/medlineplus/growthdisorders.html Hearing Disorders and Deafness http://www.nlm.nih.gov/medlineplus/hearingdisordersanddeafness.html High Risk Pregnancy http://www.nlm.nih.gov/medlineplus/highriskpregnancy.html

Within the health topic page dedicated to achondroplasia, the following was listed: •

Children Dwarfism Source: Nemours Foundation http://kidshealth.org/parent/medical/bones/dwarfism.html

•

Organizations Little People of America http://www.lpaonline.org/ National Institute of Child Health and Human Development http://www.nichd.nih.gov/

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click Search. This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The NIH Search Utility The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to achondroplasia. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for

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professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://health.nih.gov/index.asp. Under Search Health Topics, type achondroplasia (or synonyms) into the search box, and click Search. NORD (The National Organization of Rare Disorders, Inc.) NORD provides an invaluable service to the public by publishing short yet comprehensive guidelines on over 1,000 diseases. NORD primarily focuses on rare diseases that might not be covered by the previously listed sources. NORD’s Web address is http://www.rarediseases.org/. A complete guide on achondroplasia can be purchased from NORD for a nominal fee. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMD®Health: http://www.webmd.com/diseases_and_conditions/default.htm

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to achondroplasia. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with achondroplasia. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about achondroplasia. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797.

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Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://sis.nlm.nih.gov/dirline.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. Simply type in achondroplasia (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://healthhotlines.nlm.nih.gov/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type achondroplasia (or a synonym) into the search box, and click Submit Query.

Resources for Patients and Families The following are organizations that provide support and advocacy for patient with genetic conditions and their families20: •

Genetic Alliance: http://geneticalliance.org

•

Genetic and Rare Diseases Information Center: http://rarediseases.info.nih.gov/html/resources/info_cntr.html

•

Madisons Foundation: http://www.madisonsfoundation.org/

•

March of Dimes: http://www.marchofdimes.com

•

National Organization for Rare Disorders (NORD): http://www.rarediseases.org/ For More Information on Genetics

The following publications offer detailed information for patients about the science of genetics: •

What Is a Genome?: http://www.ncbi.nlm.nih.gov/About/primer/genetics_genome.html

Adapted from the National Library of Medicine: http://ghr.nlm.nih.gov/ghr/resource/patients.

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•

A Science Called Genetics: http://publications.nigms.nih.gov/genetics/science.html

•

Genetic Mapping: http://www.genome.gov/10000715

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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

•

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

•

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/archive//20040831/nichsr/ta101/ta10108.html

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on achondroplasia: •

Basic Guidelines for Achondroplasia Achondroplasia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001577.htm

•

Signs & Symptoms for Achondroplasia Frontal bossing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003301.htm Hypotonia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003298.htm Lordosis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003278.htm Polyhydramnios Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003267.htm

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Short stature Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003271.htm Skeletal (limb) abnormalities Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003170.htm Waddling gait Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003199.htm •

Diagnostics and Tests for Achondroplasia Bone X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003808.htm X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm

•

Background Topics for Achondroplasia Autosomal dominant Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002049.htm Gene Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002371.htm Genetic counseling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002053.htm hom*ozygous Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002048.htm Long bones Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002249.htm Occipital-frontal circumference Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002379.htm Proximal Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002287.htm

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

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•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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ACHONDROPLASIA DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 3-dimensional: 3-D. A graphic display of depth, width, and height. Three-dimensional radiation therapy uses computers to create a 3-dimensional picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Acanthosis Nigricans: A circ*mscribed melanosis consisting of a brown-pigmented, velvety verrucosity or fine papillomatosis appearing in the axillae and other body folds. It occurs in association with endocrine disorders, underlying malignancy, administration of certain drugs, or as in inherited disorder. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Triphosphate: Adenosine 5'-(tetrahydrogen triphosphate). An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aetiology: Study of the causes of disease. [EU] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Airway Obstruction: Any hindrance to the passage of air into and out of the lungs. [NIH] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on

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hom*ologous chromosomes, and governing the same biochemical and developmental process. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amniocentesis: Percutaneous transabdominal puncture of the uterus during pregnancy to obtain amniotic fluid. It is commonly used for fetal karyotype determination in order to diagnose abnormal fetal conditions. [NIH] Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid. [NIH]

Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Aneuploidy: The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of chromosomes or chromosome pairs. In a normally diploid cell the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is monosomy (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is trisomy (symbol: 2N+1). [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Anomalies: Birth defects; abnormalities. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anuria: Inability to form or excrete urine. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH]

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Apnea: A transient absence of spontaneous respiration. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Articular: Of or pertaining to a joint. [EU] Aseptic: Free from infection or septic material; sterile. [EU] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atresia: Lack of a normal opening from the esophagus, intestines, or anus. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Back Pain: Acute or chronic pain located in the posterior regions of the trunk, including the thoracic, lumbar, sacral, or adjacent regions. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU]

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Base Sequence: The sequence of purines and pyrimidines in nucleic acids and polynucleotides. It is also called nucleotide or nucleoside sequence. [NIH] Basem*nt Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basem*nt) lamina. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Beta-Thalassemia: A disorder characterized by reduced synthesis of the beta chains of hemoglobin. There is retardation of hemoglobin A synthesis in the heterozygous form (thalassemia minor), which is asymptomatic, while in the hom*ozygous form (thalassemia major, Cooley's anemia, Mediterranean anemia, erythroblastic anemia), which can result in severe complications and even death, hemoglobin A synthesis is absent. [NIH] Bewilderment: Impairment or loss of will power. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biogenesis: The origin of life. It includes studies of the potential basis for life in organic compounds but excludes studies of the development of altered forms of life through mutation and natural selection, which is evolution. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the

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heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Bone Development: Gross development of bones from fetus to adult. It includes osteogenesis, which is restricted to formation and development of bone from the undifferentiated cells of the germ layers of the embryo. It does not include osseointegration. [NIH]

Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Brachial: All the nerves from the arm are ripped from the spinal cord. [NIH] Brain Neoplasms: Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bupivacaine: A widely used local anesthetic agent. [NIH] Caesarean section: A surgical incision through the abdominal and uterine walls in order to deliver a baby. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carcinogenic: Producing carcinoma. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic

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hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Cataracts: In medicine, an opacity of the crystalline lens of the eye obstructing partially or totally its transmission of light. [NIH] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Centromere: The clear constricted portion of the chromosome at which the chromatids are joined and by which the chromosome is attached to the spindle during cell division. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [NIH]

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Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagin*. [NIH] Cesarean Section: Extraction of the fetus by means of abdominal hysterotomy. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Chondrocytes: Polymorphic cells that form cartilage. [NIH] Chondrogenesis: The formation of cartilage. This process is directed by chondrocytes which continually divide and lay down matrix during development. It is sometimes a precursor to osteogenesis. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chromosome Fragility: Susceptibility of chromosomes to breakage and translocation or other aberrations. Chromosome fragile sites are regions that show up in karyotypes as a gap (uncondensed stretch) on the chromatid arm. They are associated with chromosome break sites and other aberrations. A fragile site on the X chromosome is associated with fragile X syndrome. Fragile sites are designated by the letters "FRA" followed by the designation for the specific chromosome and a letter which refers to the different fragile sites on a chromosome (e.g. FRAXA). [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH]

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Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Colonoscopy: Endoscopic examination, therapy or surgery of the luminal surface of the colon. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy,

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spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Concentric: Having a common center of curvature or symmetry. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congenita: Displacement, subluxation, or malposition of the crystalline lens. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constriction: The act of constricting. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU]

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Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]

Creatine Kinase: A transferase that catalyzes formation of phosphocreatine from ATP + creatine. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic isoenzymes have been identified in human tissues: MM from skeletal muscle, MB from myocardial tissue, and BB from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins. EC 2.7.3.2. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Cyst: A sac or capsule filled with fluid. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]

Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytotoxic: Cell-killing. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Death Certificates: Official records of individual deaths including the cause of death certified by a physician, and any other required identifying information. [NIH] Decompression: Decompression external to the body, most often the slow lessening of external pressure on the whole body (especially in caisson workers, deep sea divers, and

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persons who ascend to great heights) to prevent decompression sickness. It includes also sudden accidental decompression, but not surgical (local) decompression or decompression applied through body openings. [NIH] Decompression Sickness: A condition occurring as a result of exposure to a rapid fall in ambient pressure. Gases, nitrogen in particular, come out of solution and form bubbles in body fluid and blood. These gas bubbles accumulate in joint spaces and the peripheral circulation impairing tissue oxygenation causing disorientation, severe pain, and potentially death. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Deoxyribonucleic: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleic acid: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleotides: A purine or pyrimidine base bonded to a deoxyribose containing a bond to a phosphate group. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used

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to designate a position on the dental arch farther from the median line of the jaw. [EU] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dwarfism: The condition of being undersized as a result of premature arrest of skeletal growth. It may be caused by insufficient secretion of growth hormone (pituitary dwarfism). [NIH]

Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Elastin: The protein that gives flexibility to tissues. [NIH] Electrolytes: Substances that break up into ions (electrically charged particles) when they are dissolved in body fluids or water. Some examples are sodium, potassium, chloride, and calcium. Electrolytes are primarily responsible for the movement of nutrients into cells, and the movement of wastes out of cells. [NIH] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH]

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Epiphyseal: Pertaining to or of the nature of an epiphysis. [EU] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excrete: To get rid of waste from the body. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basem*nt membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Eye Color: Color of the iris. [NIH] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Facial: Of or pertaining to the face. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fathers: Male parents, human or animal. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibril: Most bacterial viruses have a hollow tail with specialized fibrils at its tip. The tail fibers attach to the cell wall of the host. [NIH] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Flexion: In gynaecology, a displacement of the uterus in which the organ is bent so far

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forward or backward that an acute angle forms between the fundus and the cervix. [EU] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fossa: A cavity, depression, or pit. [NIH] Frameshift: A type of mutation which causes out-of-phase transcription of the base sequence; such mutations arise from the addition or delection of nucleotide(s) in numbers other than 3 or multiples of 3. [NIH] Frameshift Mutation: A type of mutation in which a number of nucleotides not divisible by three is deleted from or inserted into a coding sequence, thereby causing an alteration in the reading frame of the entire sequence downstream of the mutation. These mutations may be induced by certain types of mutagens or may occur spontaneously. [NIH] Gait: Manner or style of walking. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Expression Profiling: The determination of the pattern of genes expressed i.e., transcribed, under specific circ*mstances or in a specific cell. [NIH] Gene Products, rev: Trans-acting nuclear proteins whose functional expression are required for HIV viral replication. Specifically, the rev gene products are required for processing and translation of the HIV gag and env mRNAs, and thus rev regulates the expression of the viral structural proteins. rev can also regulate viral regulatory proteins. A cis-acting antirepression sequence (CAR) in env, also known as the rev-responsive element (RRE), is responsive to the rev gene product. rev is short for regulator of virion. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, hom*ologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity,

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particularly for leukemia. [NIH] Genes, env: DNA sequences that form the coding region for the viral envelope (env) proteins in retroviruses. The env genes contain a cis-acting RNA target sequence for the rev protein (= gene products, rev), termed the rev-responsive element (RRE). [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]

Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Germ Layers: The three layers of cells comprising the early embryo. [NIH] Germline mutation: A gene change in the body's reproductive cells (egg or sperm) that becomes incorporated into the DNA of every cell in the body of offspring; germline mutations are passed on from parents to offspring. Also called hereditary mutation. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Gliosis: The production of a dense fibrous network of neuroglia; includes astrocytosis, which is a proliferation of astrocytes in the area of a degenerative lesion. [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Granule: A small pill made from sucrose. [EU]

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Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Growth Plate: The area between the epiphysis and the diaphysis within which bone growth occurs. [NIH] Guanine: One of the four DNA bases. [NIH] Gynaecological: Pertaining to gynaecology. [EU] Hair Color: Color of hair or fur. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Hemochromatosis: A disease that occurs when the body absorbs too much iron. The body stores the excess iron in the liver, pancreas, and other organs. May cause cirrhosis of the liver. Also called iron overload disease. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobin M: A group of abnormal hemoglobins in which amino acid substitutions take place in either the alpha or beta chains but near the heme iron. This results in facilitated oxidation of the hemoglobin to yield excess methemoglobin which leads to cyanosis. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemophilia: Refers to a group of hereditary disorders in which affected individuals fail to make enough of certain proteins needed to form blood clots. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Heparan Sulfate Proteoglycan: A substance released by astrocytes, which is critical in stopping nervous fibers in their tracks. [NIH] Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular

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weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Hereditary mutation: A gene change in the body's reproductive cells (egg or sperm) that becomes incorporated into the DNA of every cell in the body of offspring; hereditary mutations are passed on from parents to offspring. Also called germline mutation. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterozygotes: Having unlike alleles at one or more corresponding loci on hom*ologous chromosomes. [NIH] Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each. [NIH] hom*ologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Human growth hormone: A protein hormone, secreted by the anterior lobe of the pituitary, which promotes growth of the whole body by stimulating protein synthesis. The human gene has already been cloned and successfully expressed in bacteria. [NIH] Humeral: 1. Of, relating to, or situated in the region of the humerus: brachial. 2. Of or belonging to the shoulder. 3. Of, relating to, or being any of several body parts that are analogous in structure, function, or location to the humerus or shoulder. [EU] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Hydrocephalus: Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial hypertension; headache; lethargy; urinary incontinence; and ataxia (and in infants macrocephaly). This condition may be caused by obstruction of cerebrospinal fluid pathways due to neurologic abnormalities, intracranial hemorrhages; central nervous system infections; brain neoplasms; craniocerebral trauma; and other conditions. Impaired resorption of cerebrospinal fluid from the arachnoid villi results in a communicating form of hydrocephalus. Hydrocephalus ex-vacuo refers to ventricular dilation that occurs as a result of brain substance loss from cerebral infarction and other conditions. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH]

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Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypotonia: A condition of diminished tone of the skeletal muscles; diminished resistance of muscles to passive stretching. [EU] Hysterotomy: An incision in the uterus, performed through either the abdomen or the vagin*. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

foreign

Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infantile: Pertaining to an infant or to infancy. [EU] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Informed Consent: Voluntary authorization, given to the physician by the patient, with full

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comprehension of the risks involved, for diagnostic or investigative procedures and medical and surgical treatment. [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intracellular: Inside a cell. [NIH] Intracranial Hemorrhages: Bleeding within the intracranial cavity, including hemorrhages in the brain and within the cranial epidural, subdural, and subarachnoid spaces. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Involuntary: Reaction occurring without intention or volition. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Isoenzyme: Different forms of an enzyme, usually occurring in different tissues. The isoenzymes of a particular enzyme catalyze the same reaction but they differ in some of their properties. [NIH] Karyotype: The characteristic chromosome complement of an individual, race, or species as defined by their number, size, shape, etc. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney Failure, Acute: A clinical syndrome characterized by a sudden decrease in glomerular filtration rate, often to values of less than 1 to 2 ml per minute. It is usually associated with oliguria (urine volumes of less than 400 ml per day) and is always associated with biochemical consequences of the reduction in glomerular filtration rate such as a rise in blood urea nitrogen (BUN) and serum creatinine concentrations. [NIH] Kidney Failure, Chronic: An irreversible and usually progressive reduction in renal function in which both kidneys have been damaged by a variety of diseases to the extent that they are unable to adequately remove the metabolic products from the blood and regulate the body's electrolyte composition and acid-base balance. Chronic kidney failure requires hemodialysis or surgery, usually kidney transplantation. [NIH] Kyphosis: A deformity of the spine characterized by extensive flexion. [NIH]

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Laryngoscopy: Examination, therapy, or surgery of the interior of the larynx performed with a specially designed endoscope. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]

Leukaemia: An acute or chronic disease of unknown cause in man and other warm-blooded animals that involves the blood-forming organs, is characterized by an abnormal increase in the number of leucocytes in the tissues of the body with or without a corresponding increase of those in the circulating blood, and is classified according of the type leucocyte most prominently involved. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Linkages: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipomatosis: A disorder consisting of the accumulation of abnormal localized, or tumor-like fat in the tissues. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B

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(with subpopulations of each); those with characteristics of neither major class are called null cells. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Malformation: A morphologic developmental process. [EU]

defect

resulting

from

intrinsically

abnormal

Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Mammography: Radiographic examination of the breast. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Megakaryocytes: Very large bone marrow cells which release mature blood platelets. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Melanosis: Disorders of increased melanin pigmentation that develop without preceding inflammatory disease. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that

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cannot be properly seen by the unaided eye. [NIH] Miscarriage: Spontaneous expulsion of the products of pregnancy before the middle of the second trimester. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monosomy: The condition in which one chromosome of a pair is missing. In a normally diploid cell it is represented symbolically as 2N-1. [NIH] Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH]

Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Mosaicism: The occurrence in an individual of two or more cell populations of different chromosomal constitutions, derived from a single zygote, as opposed to chimerism in which the different cell populations are derived from more than one zygote. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Nail-Patella Syndrome: A syndrome of multiple abnormalities characterized by the absence or hypoplasia of the patella and congenital nail dystrophy. It is a genetically determined autosomal dominant trait. [NIH] Natural selection: A part of the evolutionary process resulting in the survival and reproduction of the best adapted individuals. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis,

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prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neonatal period: The first 4 weeks after birth. [NIH] Nephropathy: Disease of the kidneys. [EU] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neuralgia: Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Envelope: The membrane system of the cell nucleus that surrounds the nucleoplasm. It consists of two concentric membranes separated by the perinuclear space. The structures of the envelope where it opens to the cytoplasm are called the nuclear pores (nuclear pore). [NIH] Nuclear Pore: An opening through the nuclear envelope formed by the nuclear pore complex which transports nuclear proteins or RNA into or out of the cell nucleus and which, under some conditions, acts as an ion channel. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nurse Practitioners: Nurses who are specially trained to assume an expanded role in providing medical care under the supervision of a physician. [NIH] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH]

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Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Disk: The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. [NIH]

Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Osseointegration: The growth action of bone tissue, as it assimilates surgically implanted devices or prostheses to be used as either replacement parts (e.g., hip) or as anchors (e.g., endosseous dental implants). [NIH] Ossification: The formation of bone or of a bony substance; the conversion of fibrous tissue or of cartilage into bone or a bony substance. [EU] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Osteoblasts: Bone-forming cells which secrete an extracellular matrix. Hydroxyapatite crystals are then deposited into the matrix to form bone. [NIH] Osteochondrodysplasias: Abnormal development of cartilage and bone. [NIH] Osteogenesis: The histogenesis of bone including ossification. It occurs continuously but particularly in the embryo and child and during fracture repair. [NIH] Osteogenesis Imperfecta: A collagen disorder resulting from defective biosynthesis of type I collagen and characterized by brittle, osteoporotic, and easily fractured bones. It may also present with blue sclerae, loose joints, and imperfect dentin formation. There are four major types, I-IV. [NIH] Osteotomy: The surgical cutting of a bone. [EU] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidative Phosphorylation: Electron transfer through the cytochrome system liberating free energy which is transformed into high-energy phosphate bonds. [NIH] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Papilledema: Swelling around the optic disk. [NIH] Patella: The flat, triangular bone situated at the anterior part of the knee. [NIH] Paternal Age: Age of the father. [NIH] Paternity: Establishing the father relationship of a man and a child. [NIH]

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Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [NIH] PDQ: Physician Data Query. PDQ is an online database developed and maintained by the National Cancer Institute. Designed to make the most current, credible, and accurate cancer information available to health professionals and the public, PDQ contains peer-reviewed summaries on cancer treatment, screening, prevention, genetics, and supportive care; a registry of cancer clinical trials from around the world; and directories of physicians, professionals who provide genetics services, and organizations that provide cancer care. Most of this information is available on the CancerNet Web site, and more specific information about PDQ can be found at http://cancernet.nci.nih.gov/pdq.html. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs

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of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigments: Any normal or abnormal coloring matter in plants, animals, or micro-organisms. [NIH]

Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH]

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Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circ*mstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prenatal Diagnosis: Determination of the nature of a pathological condition or disease in the postimplantation embryo, fetus, or pregnant female before birth. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Prone: Having the front portion of the body downwards. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and

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editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH]

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Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]

Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal Osteodystrophy: Decalcification of bone due to hyperparathyroidism secondary to chronic kidney disease. [NIH] Reproductive cells: Egg and sperm cells. Each mature reproductive cell carries a single set of 23 chromosomes. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory failure: Inability of the lungs to conduct gas exchange. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retraction: 1. The act of drawing back; the condition of being drawn back. 2. Distal movement of teeth, usually accomplished with an orthodontic appliance. [EU] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Rhodopsin: A photoreceptor protein found in retinal rods. It is a complex formed by the binding of retinal, the oxidized form of retinol, to the protein opsin and undergoes a series of complex reactions in response to visible light resulting in the transmission of nerve impulses to the brain. [NIH] Ribonucleic acid: RNA. One of the two nucleic acids found in all cells. The other is deoxyribonucleic acid (DNA). Ribonucleic acid transfers genetic information from DNA to proteins produced by the cell. [NIH]

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Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rod: A reception for vision, located in the retina. [NIH] Scatter: The extent to which relative success and failure are divergently manifested in qualitatively different tests. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Sclerae: A circular furrow between the sclerocorneal junction and the iris. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skin Pigmentation: Coloration of the skin. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the

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brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Work: The use of community resources, individual case work, or group work to promote the adaptive capacities of individuals in relation to their social and economic environments. It includes social service agencies. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] Somatic mutations: Alterations in DNA that occur after conception. Somatic mutations can occur in any of the cells of the body except the germ cells (sperm and egg) and therefore are not passed on to children. These alterations can (but do not always) cause cancer or other diseases. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Sperm: The fecundating fluid of the male. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Stenosis: Narrowing of the spinal canal. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stenosis: Narrowing or stricture of a duct or canal. [EU] Stillbirth: The birth of a dead fetus or baby. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH]

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Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Sudden death: Cardiac arrest caused by an irregular heartbeat. The term "death" is somewhat misleading, because some patients survive. [NIH] Supportive care: Treatment given to prevent, control, or relieve complications and side effects and to improve the comfort and quality of life of people who have cancer. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of hom*ologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synostosis: The joining of contiguous and separate bones by osseous tissue. [NIH] Syringomyelia: The presence in the spinal cord of elongated central fluid containing cavities surrounded by gliosis. [NIH] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Thalassemia: A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia. [NIH] Thanatophoric Dysplasia: A severe form of neonatal dwarfism with very short limbs. All cases have died at birth or in the neonatal period. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thoracic: Having to do with the chest. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH]

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Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombopoietin: A humoral factor that controls blood platelet production through stimulation of megakaryocyte populations. Bone marrow megakaryocytes increase in both size and number in response to exposure to thrombopoietin. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual,

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between individuals of the same species, or between individuals of different species. [NIH] Trinucleotide Repeat Expansion: DNA region comprised of a variable number of repetitive, contiguous trinucleotide sequences. The presence of these regions is associated with diseases such as Fragile X Syndrome and myotonic dystrophy. Many chromosome fragile sites (chromosome fragility) contain expanded trinucleotide repeats. [NIH] Trinucleotide Repeats: Microsatellite repeats consisting of three nucleotides dispersed in the euchromatic arms of chromosomes. [NIH] Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [NIH]

Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Ultraviolet radiation: Invisible rays that are part of the energy that comes from the sun. UV radiation can damage the skin and cause melanoma and other types of skin cancer. UV radiation that reaches the earth's surface is made up of two types of rays, called UVA and UVB rays. UVB rays are more likely than UVA rays to cause sunburn, but UVA rays pass deeper into the skin. Scientists have long thought that UVB radiation can cause melanoma and other types of skin cancer. They now think that UVA radiation also may add to skin damage that can lead to skin cancer and cause premature aging. For this reason, skin specialists recommend that people use sunscreens that reflect, absorb, or scatter both kinds of UV radiation. [NIH] Umbilical Cord: The flexible structure, giving passage to the umbilical arteries and vein, which connects the embryo or fetus to the placenta. [NIH] Umbilicus: The pit in the center of the abdominal wall marking the point where the umbilical cord entered in the fetus. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] vagin*: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU]

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VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venter: Belly. [NIH] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Ventriculostomy: Surgical creation of an opening in a cerebral ventricle. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] War: Hostile conflict between organized groups of people. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH]

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Wound Healing: Restoration of integrity to traumatized tissue. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

154

INDEX 3 3-dimensional, 73, 104, 118 A Abdomen, 118, 135, 137, 142, 148, 152 Abdominal, 57, 118, 122, 124, 141, 151 Aberrant, 23, 118 Acanthosis Nigricans, 6, 9, 11, 55, 56, 58, 118 Adaptability, 118, 123 Adenine, 67, 118, 145 Adenosine, 68, 118, 142 Adenosine Triphosphate, 68, 118, 142 Adenovirus, 100, 118 Adverse Effect, 118, 147 Aerobic, 118, 139 Aetiology, 17, 118 Airway, 55, 118, 148 Airway Obstruction, 55, 118 Alanine, 8, 118 Algorithms, 118, 121 Alkaline, 118, 122 Alleles, 15, 69, 86, 118, 134 Alpha-1, 82, 86, 119 Alternative medicine, 119 Amino Acids, 8, 9, 69, 73, 79, 119, 125, 142, 143, 144, 147, 150 Amniocentesis, 52, 119 Amnion, 119 Amniotic Fluid, 95, 97, 119 Ampulla, 119, 129 Anaesthesia, 22, 31, 39, 119 Analogous, 119, 134, 150 Anatomical, 119, 124, 135, 147 Anemia, 13, 81, 82, 85, 86, 91, 119, 121, 149 Anesthesia, 31, 118, 119 Aneuploidy, 80, 119 Annealing, 119, 143 Anomalies, 28, 119 Anticoagulant, 119, 144 Anuria, 119, 136 Anus, 119, 120, 125, 136 Apnea, 4, 27, 120 Apoptosis, 11, 68, 77, 120 Aqueous, 120, 127, 137 Arginine, 8, 9, 120, 134 Arterial, 120, 123, 135, 144, 149 Arteries, 120, 122, 126, 127, 145, 151 Arterioles, 120, 122 Articular, 14, 120, 141

Aseptic, 120, 141 Assay, 53, 120 Astrocytes, 120, 132, 133 Asymptomatic, 120, 121 Ataxia, 120, 134 Atresia, 25, 120 Atypical, 90, 120 B Back Pain, 4, 120 Bacteria, 66, 74, 78, 120, 130, 134, 138, 150, 151 Base, 9, 10, 16, 67, 68, 71, 73, 77, 78, 79, 102, 118, 120, 121, 127, 128, 131, 136, 143, 149 Base Sequence, 78, 121, 131 Basem*nt Membrane, 121, 130 Benign, 33, 121, 122, 133 Beta-Thalassemia, 13, 121 Bewilderment, 121, 126 Bilateral, 23, 33, 121 Bile, 121, 131, 137 Biochemical, 13, 15, 16, 38, 82, 119, 121, 132, 136, 141 Biogenesis, 14, 121 Biological therapy, 121, 133 Biosynthesis, 121, 141 Biotechnology, 18, 73, 100, 102, 107, 121 Bladder, 9, 10, 11, 61, 121, 135, 151 Blastocyst, 121, 126 Blood Coagulation, 121, 122, 150 Blood Glucose, 121, 133 Blood Platelets, 121, 138, 150 Blood pressure, 85, 121, 122, 135, 139, 145 Blood vessel, 7, 89, 121, 122, 124, 129, 138, 148, 149, 150, 151 Bone Development, 12, 15, 17, 122 Bone Marrow, 101, 122, 131, 137, 138 Brachial, 122, 134 Brain Neoplasms, 122, 134 Buccal, 95, 97, 122 Bupivacaine, 31, 122 C Caesarean section, 31, 122 Calcium, 45, 122, 125, 129, 147 Callus, 58, 122 Carbohydrate, 39, 122, 132 Carcinogenic, 122, 136 Cardiovascular, 13, 104, 122 Cardiovascular disease, 13, 104, 122

Index 155

Carotene, 122, 146 Case report, 21, 22, 24, 28, 32, 33, 39, 51, 57, 60, 61, 123 Cataracts, 14, 123 Cause of Death, 123, 127 Cell Cycle, 76, 77, 123 Cell Death, 77, 120, 123, 140 Cell Differentiation, 123, 147 Cell Division, 9, 69, 76, 77, 89, 90, 120, 123, 133, 138, 139, 143 Cell membrane, 7, 9, 123, 128 Cell proliferation, 123, 147 Cell Respiration, 123, 139, 146 Cell Survival, 123, 133 Central Nervous System, 118, 122, 123, 131, 132, 133, 134 Central Nervous System Infections, 123, 133, 134 Centromere, 69, 72, 123 Cerebral, 120, 122, 123, 129, 134, 152 Cerebral Infarction, 123, 134 Cerebrospinal, 124, 134 Cerebrospinal fluid, 124, 134 Cerebrovascular, 122, 124 Cervical, 21, 34, 61, 124 Cervix, 10, 124, 131 Cesarean Section, 31, 124 Chin, 25, 124, 138 Cholesterol, 68, 121, 124, 127 Chondrocytes, 9, 14, 15, 16, 124, 130 Chondrogenesis, 14, 35, 124 Chromatin, 120, 124, 137 Chromosomal, 47, 52, 77, 79, 80, 90, 91, 92, 94, 119, 124, 134, 139 Chromosome Fragility, 124, 151 Chronic, 23, 30, 120, 124, 135, 136, 137, 146 Chronic Disease, 124, 137 Cirrhosis, 124, 133 CIS, 124, 131, 132, 146 Clinical Medicine, 103, 124, 144 Clinical trial, 11, 100, 101, 104, 107, 124, 142, 144 Cloning, 121, 125 Codon, 74, 125 Cofactor, 125, 144, 150 Collagen, 14, 17, 30, 121, 125, 130, 141, 144 Collapse, 125, 148 Colon, 83, 125 Colonoscopy, 85, 125 Complement, 125, 126, 136 Complementary and alternative medicine, 62, 64, 125

Complementary medicine, 62, 126 Computational Biology, 107, 126 Computed tomography, 43, 126 Computerized axial tomography, 126 Computerized tomography, 126 Concentric, 126, 140 Conception, 76, 126, 130, 148 Cones, 126, 146 Confusion, 83, 126, 128, 151 Congenita, 41, 43, 45, 49, 126 Connective Tissue, 12, 111, 122, 125, 126, 130, 131, 137, 138 Connective Tissue Cells, 126 Consciousness, 126, 128 Constriction, 69, 72, 126 Consultation, 91, 92, 95, 96, 126 Contraindications, ii, 126 Coronary, 122, 126, 127 Coronary heart disease, 122, 127 Cranial, 12, 16, 127, 133, 136, 140, 142 Craniocerebral Trauma, 127, 133, 134 Creatine, 42, 127 Creatine Kinase, 42, 127 Creatinine, 127, 136 Cyst, 22, 127 Cysteine, 9, 127 Cystine, 127 Cytochrome, 27, 127, 141 Cytoplasm, 66, 67, 68, 74, 120, 123, 127, 133, 137, 140, 147 Cytosine, 67, 127, 145 Cytotoxic, 127, 147 D De novo, 13, 60, 77, 127 Death Certificates, 85, 127 Decompression, 25, 27, 32, 33, 43, 51, 127, 128 Decompression Sickness, 128 Degenerative, 128, 132, 141 Deletion, 79, 120, 128 Dementia, 80, 128 Denaturation, 128, 143 Deoxyribonucleic, 67, 128, 146 Deoxyribonucleic acid, 67, 128, 146 Deoxyribonucleotides, 128 Depolarization, 128, 147 Diabetes Mellitus, 128, 133 Diagnostic procedure, 128 Diastolic, 128, 135 Digestion, 121, 128, 137, 148, 151 Dilation, 128, 134 Dimerization, 12, 16, 57, 128

156

Achondroplasia

Diploid, 45, 119, 128, 139, 143, 151 Direct, iii, 39, 95, 96, 97, 124, 128, 145 Discrimination, 98, 103, 128 Disorientation, 126, 128 Distal, 43, 128, 144, 146 Dorsal, 12, 129, 143 Dorsum, 129 Duct, 119, 129, 148 Duodenum, 121, 129, 148 Dwarfism, 4, 5, 6, 7, 10, 15, 16, 28, 29, 32, 46, 59, 63, 111, 129, 149 Dysplasia, 5, 9, 10, 13, 14, 17, 23, 41, 43, 45, 49, 50, 55, 57, 60, 129 Dystrophy, 26, 129, 139 E Elastin, 125, 129 Electrolytes, 121, 129, 136 Electrons, 120, 129, 136, 145 Embryo, 7, 10, 12, 76, 77, 78, 86, 119, 121, 122, 123, 129, 132, 141, 144, 151 Endemic, 129, 148 Endoscope, 129, 137 Endoscopic, 59, 125, 129 Endothelial cell, 129, 130, 150 Environmental Health, 106, 107, 129 Enzymatic, 122, 123, 125, 129, 143, 146 Enzyme, 68, 74, 129, 131, 136, 143, 144, 147, 149, 150, 152, 153 Epidemic, 129, 148 Epinephrine, 129, 140, 151 Epiphyseal, 17, 50, 130 Erythrocytes, 119, 122, 130 Esophagus, 120, 130, 148 Ethnic Groups, 91, 94, 130 Eukaryotic Cells, 130, 141 Excitatory, 130, 132 Excrete, 119, 130, 136 Extracellular, 12, 14, 17, 120, 126, 130, 141 Extracellular Matrix, 14, 17, 126, 130, 141 Extracellular Space, 130 Extremity, 22, 29, 130 Eye Color, 78, 130 Eye Infections, 118, 130 F Facial, 31, 63, 130 Family Planning, 107, 130 Fat, 122, 127, 130, 137, 148 Fathers, 13, 86, 130 Femur, 39, 130 Fetus, 94, 95, 97, 101, 122, 124, 130, 144, 148, 151 Fibril, 14, 130

Fibroblast Growth Factor, 6, 7, 8, 9, 10, 11, 15, 16, 19, 25, 26, 27, 35, 45, 46, 51, 55, 57, 58, 130 Fibroblasts, 17, 45, 126, 130 Fibrosis, 78, 81, 85, 86, 130, 147 Flexion, 130, 136 Fluorescence, 17, 53, 131 Foramen, 16, 19, 25, 32, 33, 36, 44, 124, 131 Forearm, 122, 131 Fossa, 51, 131 Frameshift, 79, 131 Frameshift Mutation, 79, 131 G Gait, 116, 131 Gallbladder, 118, 131 Ganglia, 120, 122, 131, 140, 142 Gas, 128, 131, 134, 146, 152 Gas exchange, 131, 146 Gastrin, 131, 134 Gene Expression, 14, 74, 75, 131 Gene Expression Profiling, 14, 131 Gene Products, rev, 131, 132 Gene Therapy, 99, 100, 101, 102, 118, 131 Genes, env, 85, 132 Genetic testing, 40, 88, 92, 93, 94, 95, 96, 97, 98, 103, 132, 143 Genomics, 104, 132 Genotype, 17, 29, 31, 34, 48, 132, 142 Germ Cells, 77, 101, 132, 138, 148 Germ Layers, 122, 132 Germline mutation, 13, 77, 132, 134 Gestation, 60, 132, 142 Gland, 132, 137, 141, 143, 147, 150 Gliosis, 132, 149 Glucose, 121, 128, 132, 133 Glucuronic Acid, 132, 133 Glutamate, 132 Glutamic Acid, 8, 132, 140, 144 Glycine, 8, 132, 140 Glycosylation, 39, 132 Governing Board, 132, 144 Grade, 10, 132 Granule, 132, 147 Granulocytes, 133, 137, 147, 152 Growth factors, 7, 12, 133 Growth Plate, 37, 133 Guanine, 67, 133, 145 Gynaecological, 52, 133 H Hair Color, 78, 133 Headache, 133, 134 Health Status, 33, 133

Index 157

Heart attack, 122, 133 Heartbeat, 133, 149 Hemochromatosis, 94, 133 Hemodialysis, 133, 136 Hemoglobin, 68, 119, 121, 130, 133, 149 Hemoglobinopathies, 13, 131, 133 Hemophilia, 86, 133 Hemorrhage, 40, 51, 127, 133, 149 Heparan Sulfate Proteoglycan, 12, 133 Heparin, 12, 133 Hereditary, 14, 66, 67, 77, 86, 92, 132, 133, 134, 146, 149 Hereditary mutation, 77, 132, 134 Heredity, 69, 131, 132, 134 Heterozygotes, 60, 134 Histones, 69, 124, 134 hom*ologous, 119, 131, 134, 149 Hormone, 29, 31, 35, 36, 44, 45, 46, 50, 54, 57, 59, 74, 129, 131, 134, 147, 150 Hormone therapy, 29, 35, 36, 134 Human growth hormone, 36, 38, 55, 134 Humeral, 23, 134 Humoral, 134, 150 Hydrocephalus, 38, 39, 44, 59, 134, 136 Hydrogen, 120, 122, 128, 134, 139 Hydroxylysine, 125, 134 Hydroxyproline, 125, 135 Hypertension, 39, 122, 135, 136 Hypoplasia, 16, 43, 63, 135, 139 Hypothalamic, 29, 135 Hypothalamus, 122, 135, 143 Hypotonia, 19, 115, 135 Hysterotomy, 124, 135 I Immune response, 135, 149, 152 Immune system, 121, 135, 138, 151, 152 Immunity, 118, 135 Impairment, 51, 120, 121, 130, 135, 138 Implantation, 126, 135 In situ, 17, 135 In vitro, 12, 14, 17, 131, 135, 143 In vivo, 12, 16, 17, 131, 134, 135 Incision, 122, 135 Incontinence, 134, 135 Infancy, 37, 63, 104, 135 Infantile, 19, 135 Infection, 120, 121, 130, 135, 137, 140, 152 Inflammation, 100, 130, 135, 143 Informed Consent, 95, 98, 103, 135 Initiation, 17, 136, 150 Insight, 12, 136 Intestines, 118, 120, 136

Intracellular, 12, 16, 135, 136, 147 Intracranial Hemorrhages, 134, 136 Intracranial Hypertension, 133, 134, 136 Involuntary, 136, 148 Ions, 120, 129, 134, 136 Iris, 130, 136, 147 Isoenzyme, 127, 136 K Karyotype, 21, 71, 119, 136 Kidney Disease, 51, 106, 136, 146 Kidney Failure, 80, 136 Kidney Failure, Acute, 136 Kidney Failure, Chronic, 136 Kyphosis, 40, 41, 51, 53, 56, 57, 60, 136 L Laryngoscopy, 39, 137 Larynx, 137, 150 Latent, 12, 137 Lens, 15, 123, 126, 137 Lesion, 132, 137 Lethal, 9, 10, 11, 41, 137 Lethargy, 134, 137 Leucocyte, 119, 137 Leukaemia, 20, 137 Leukemia, 23, 132, 137 Linkages, 133, 134, 137 Lipomatosis, 20, 137 Liver, 75, 118, 121, 124, 131, 132, 133, 134, 137 Lobe, 123, 134, 137 Localization, 43, 47, 137 Localized, 135, 137, 143 Lumbar, 34, 40, 41, 45, 46, 57, 60, 120, 137 Lymph, 124, 129, 137 Lymph node, 124, 137 Lymphatic, 135, 137, 138 Lymphocytes, 137, 152 Lysine, 8, 9, 134, 138 M Macrophage, 77, 138 Malformation, 51, 138 Malignancy, 118, 138 Mammography, 85, 138 Mediate, 15, 16, 138 Medical Records, 85, 98, 138 MEDLINE, 107, 138 Medullary, 43, 44, 138 Megakaryocytes, 138, 150 Meiosis, 76, 138, 149 Melanin, 136, 138, 142, 151 Melanoma, 138, 151 Melanosis, 118, 138

158

Achondroplasia

Membrane, 16, 67, 119, 120, 123, 125, 128, 130, 137, 138, 140, 141, 146, 147 Memory, 128, 138 Mental, iv, 11, 14, 37, 90, 92, 94, 106, 108, 124, 126, 128, 138, 144, 147, 151 Mental Health, iv, 11, 106, 108, 138, 144 Mental Retardation, 14, 90, 92, 94, 138 Mesenchymal, 15, 63, 138 Microbe, 138, 150 Microbiology, 15, 120, 138 Microorganism, 125, 138, 152 Microscopy, 14, 17, 121, 138 Miscarriage, 97, 139 Mitochondria, 67, 68, 80, 86, 87, 139, 141 Mitosis, 76, 120, 139 Modeling, 17, 139 Modification, 139, 145 Molecule, 67, 68, 69, 74, 120, 125, 139, 143, 145, 147, 152 Monitor, 127, 139, 140 Monosomy, 80, 119, 139 Morphogenesis, 15, 139 Morphological, 129, 139 Morphology, 55, 139 Mosaicism, 34, 77, 139 Mutagenesis, 17, 139 Mutagens, 131, 139 Myotonic Dystrophy, 89, 139, 151 N Nail-Patella Syndrome, 20, 139 Natural selection, 121, 139 NCI, 1, 105, 124, 139, 142 Necrosis, 120, 123, 140 Neonatal, 140, 149 Neonatal period, 140, 149 Nephropathy, 136, 140 Nervous System, 29, 38, 57, 59, 89, 123, 140, 142 Neuralgia, 60, 140 Neurologic, 24, 47, 134, 140 Neurology, 23, 27, 40, 47, 60, 63, 140 Neuropathy, 86, 140 Neurotransmitter, 118, 132, 140, 147, 149 Nuclear, 67, 129, 130, 131, 140 Nuclear Envelope, 67, 140 Nuclear Pore, 140 Nuclei, 129, 131, 134, 139, 140 Nucleic acid, 121, 127, 139, 140, 145, 146 Nucleus, 67, 68, 69, 74, 80, 99, 102, 120, 124, 127, 130, 137, 138, 140, 149 Nurse Practitioners, 95, 140

O Oliguria, 136, 140 Opacity, 123, 140 Opsin, 141, 146 Optic Disk, 141 Organ Culture, 15, 141 Organelles, 66, 67, 127, 141, 143 Osseointegration, 122, 141 Ossification, 4, 7, 16, 61, 141 Osteoarthritis, 14, 141 Osteoblasts, 15, 141 Osteochondrodysplasias, 17, 141 Osteogenesis, 29, 35, 40, 63, 122, 124, 141 Osteogenesis Imperfecta, 29, 40, 141 Osteotomy, 51, 141 Ovaries, 94, 141 Ovum, 132, 141, 152, 153 Oxidative Phosphorylation, 68, 141 P Palsy, 31, 141 Pancreas, 118, 133, 141 Papilledema, 59, 141 Patella, 139, 141 Paternal Age, 29, 58, 141 Paternity, 94, 141 Pathologic, 120, 126, 142, 146 Pathologic Processes, 120, 142 Pathophysiology, 15, 38, 142 Patient Selection, 41, 142 PDQ, 105, 142 Pelvic, 20, 142 Pelvis, 118, 137, 141, 142, 151 Peptide, 62, 130, 142, 143, 144 Perforation, 131, 142 Perinatal, 60, 142 Peripheral Nervous System, 140, 141, 142, 149 Pharmacologic, 119, 142, 150 Phenotype, 12, 14, 15, 16, 17, 20, 31, 33, 34, 44, 49, 142 Phenylalanine, 74, 142, 151 Phospholipases, 142, 147 Phosphorus, 122, 142 Phosphorylation, 68, 142 Physical Examination, 92, 142 Physiologic, 121, 143, 145, 146 Physiology, 12, 143 Pigments, 122, 143, 146 Pituitary Gland, 130, 143 Plants, 132, 139, 143 Plasma, 16, 39, 63, 67, 118, 123, 133, 136, 143

Index 159

Plastids, 141, 143 Platelet Activation, 143, 147 Pneumonia, 126, 143 Point Mutation, 27, 39, 143 Polymerase, 52, 143 Polymerase Chain Reaction, 52, 143 Polymorphism, 96, 143 Polypeptide, 125, 143, 149, 153 Posterior, 51, 120, 129, 136, 141, 143 Postnatal, 26, 143, 148 Postsynaptic, 143, 147 Potentiation, 144, 147 Practice Guidelines, 108, 144 Precursor, 124, 129, 142, 144, 151 Prenatal, 26, 30, 31, 32, 39, 40, 43, 45, 52, 60, 94, 97, 129, 144 Prenatal Diagnosis, 26, 30, 31, 32, 39, 40, 43, 45, 52, 60, 144 Prevalence, 23, 82, 144 Progression, 17, 144 Progressive, 80, 123, 124, 128, 136, 139, 140, 141, 143, 144 Proline, 8, 125, 135, 144 Prone, 80, 89, 144 Proteolytic, 119, 125, 144 Protocol, 100, 144 Proximal, 116, 128, 144 Psychic, 138, 144 Public Health, 16, 25, 108, 144 Public Policy, 107, 144 Publishing, 112, 144 Pulmonary, 43, 55, 121, 136, 145, 152 Pulmonary Artery, 121, 145, 152 Pulmonary Edema, 136, 145 Pulmonary hypertension, 43, 55, 145 Purines, 121, 145 Pyrimidines, 121, 145 Q Quality of Life, 42, 43, 145, 149 R Race, 136, 145 Radiation, 118, 131, 145, 151, 153 Radiation therapy, 118, 145 Radioactive, 134, 135, 140, 145 Radiological, 15, 26, 145 Radiology, 19, 20, 22, 25, 38, 50, 145 Receptor, 6, 7, 8, 9, 10, 11, 12, 14, 16, 19, 25, 26, 27, 32, 35, 45, 46, 51, 55, 57, 58, 83, 145, 147 Recombinant, 55, 100, 145, 152 Recombination, 131, 145 Rectum, 119, 125, 131, 135, 145

Recurrence, 31, 33, 54, 145 Refer, 1, 72, 76, 78, 83, 102, 122, 125, 137, 145 Regeneration, 130, 146 Reliability, 22, 146 Remission, 145, 146 Renal Osteodystrophy, 24, 146 Reproductive cells, 80, 90, 91, 132, 134, 146 Resorption, 134, 146 Respiration, 120, 139, 146 Respiratory failure, 4, 18, 146 Retina, 126, 137, 146, 147 Retinal, 26, 141, 146 Retinoblastoma, 82, 146 Retinol, 146 Retraction, 26, 146 Retroviral vector, 131, 146 Rhodopsin, 141, 146 Ribonucleic acid, 74, 146 Ribose, 118, 147 Ribosome, 74, 147, 150 Rod, 26, 147 S Scatter, 147, 151 Schizophrenia, 87, 147 Sclerae, 141, 147 Sclerosis, 83, 147 Screening, 43, 49, 85, 94, 95, 97, 124, 142, 147 Secretion, 50, 54, 129, 147, 151 Sensibility, 119, 147 Sequencing, 102, 143, 147 Serum, 30, 42, 125, 127, 136, 147 Side effect, 101, 104, 118, 121, 147, 149, 150 Signal Transduction, 15, 147 Signs and Symptoms, 8, 88, 89, 94, 146, 147 Skeletal, 4, 5, 6, 9, 10, 11, 12, 13, 14, 15, 16, 20, 41, 55, 58, 116, 127, 129, 135, 147, 148 Skeleton, 130, 147 Skin Pigmentation, 8, 147 Skull, 8, 9, 127, 147, 149 Sleep apnea, 48, 50, 54, 60, 148 Small intestine, 129, 134, 136, 148, 152 Smooth muscle, 126, 148, 149 Social Environment, 145, 148 Social Work, 91, 148 Soft tissue, 30, 122, 147, 148 Soma, 148 Somatic, 9, 34, 77, 80, 91, 134, 138, 139, 142, 148 Somatic cells, 77, 80, 91, 138, 139, 148

160

Achondroplasia

Somatic mutations, 9, 80, 148 Spasm, 28, 148 Specialist, 95, 112, 128, 148 Species, 13, 104, 129, 136, 138, 139, 145, 148, 149, 151, 152 Sperm, 13, 58, 76, 77, 80, 89, 90, 91, 94, 101, 124, 132, 134, 146, 148 Spinal cord, 120, 122, 123, 124, 140, 142, 148, 149 Spinal Stenosis, 24, 30, 34, 57, 148 Sporadic, 13, 33, 46, 54, 146, 148 Stem Cells, 13, 15, 63, 148 Stenosis, 25, 27, 33, 40, 45, 57, 60, 61, 148, 149 Stillbirth, 92, 148 Stomach, 118, 130, 131, 134, 136, 148 Stool, 125, 135, 149 Strand, 67, 143, 149 Stricture, 148, 149 Stroke, 85, 106, 122, 149 Subspecies, 148, 149 Sudden death, 16, 149 Supportive care, 142, 149 Synaptic, 140, 147, 149 Synostosis, 52, 149 Syringomyelia, 22, 149 Systemic, 122, 129, 135, 136, 145, 149 Systolic, 135, 149 T Temporal, 27, 37, 149 Terminator, 125, 149 Thalassemia, 121, 149 Thanatophoric Dysplasia, 9, 10, 11, 13, 16, 23, 26, 29, 35, 44, 45, 46, 49, 149 Thermal, 143, 149 Thoracic, 120, 149, 152 Threshold, 135, 149 Thrombin, 144, 149, 150 Thrombocytopenia, 30, 150 Thrombomodulin, 144, 150 Thrombopoietin, 30, 150 Thrombosis, 144, 149, 150 Thyroid, 94, 150, 151 Thyroid Gland, 94, 150 Thyroid Hormones, 150, 151 Tissue, 4, 7, 15, 95, 97, 99, 118, 121, 122, 126, 127, 128, 130, 135, 137, 138, 141, 143, 146, 147, 148, 149, 150, 153 Tomography, 150 Tone, 135, 150 Toxic, iv, 66, 135, 140, 150 Toxicity, 100, 150

Toxicology, 107, 150 Trachea, 137, 150 Transcription Factors, 75, 150 Transduction, 147, 150 Transfection, 121, 131, 150 Transferases, 132, 150 Translation, 74, 75, 131, 150 Transplantation, 23, 63, 136, 150 Trinucleotide Repeat Expansion, 89, 151 Trinucleotide Repeats, 151 Trisomy, 80, 119, 151 Tryptophan, 125, 151 Tyrosine, 12, 16, 151 U Ultrasonography, 52, 151 Ultraviolet radiation, 77, 151 Umbilical Cord, 151 Umbilicus, 61, 151 Uremia, 136, 151 Urinary, 134, 135, 140, 151 Urine, 61, 119, 121, 127, 135, 136, 140, 151 Uterus, 94, 119, 124, 130, 135, 141, 151 V Vaccine, 144, 151 Vacuoles, 141, 151 vagin*, 124, 135, 151 Vascular, 61, 135, 150, 151 Vector, 99, 100, 150, 152 Vein, 140, 151, 152 Venous, 39, 44, 123, 144, 152 Venter, 152 Ventral, 12, 135, 152 Ventricle, 135, 145, 149, 152 Ventricular, 61, 134, 152 Ventriculostomy, 59, 152 Venules, 122, 152 Vertebral, 59, 152 Veterinary Medicine, 107, 152 Villi, 134, 152 Viral, 99, 131, 132, 150, 152 Virulence, 150, 152 Virus, 99, 123, 146, 150, 152 Viscera, 148, 152 Vitreous, 137, 146, 152 Vitro, 14, 18, 94, 134, 152 Vivo, 18, 152 W War, 152 White blood cell, 77, 137, 138, 152 Windpipe, 150, 152 Womb, 151, 152 Wound Healing, 7, 130, 153

Index 161

X X-ray, 116, 126, 131, 140, 145, 153 Y Yeasts, 142, 153

Z Zygote, 126, 139, 153 Zymogen, 144, 153

Achondroplasia - A Bibliography and Dictionary for Physicians, Patients, and Genome Researchers - PDF Free Download (2024)

FAQs

Is achondroplasia the same as dwarfism? ›

Achondroplasia is the most common type of dwarfism. Achondroplasia is a genetic condition that affects about 1 in 15,000 to 1 in 40,000 people. It makes your arms and legs short in comparison to your head and trunk.

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What is the current research on achondroplasia? ›

Scientists are studying 2 main types of therapies:

CNP activates the NPR-B receptors (natriuretic peptide receptor-B), reducing the effects of the overactive FGFR3 receptors which tell the bones to stop growing.

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What is the genome of achondroplasia? ›

Achondroplasia results from a point mutation in the gene coding for the transmembrane portion of fibroblast growth factor receptor 3 (FGFR3), which resides on the short arm of chromosome 4.

Does achondroplasia come from mother or father? ›

Achondroplasia may be inherited as an autosomal dominant trait. This means that if a child gets the defective gene from one parent, the child will have the disorder. If one parent has achondroplasia, the infant has a 50% chance of inheriting the disorder.

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Can achondroplasia be cured? ›

Achondroplasia is the result of a mutation in the FGFR3 gene and might be detected using radiological techniques, physical exams and genetic testing. Treatment of symptoms might include monitoring and surgery by doctors who specialize in skeletal dysplasia. There is no cure for achondroplasia.

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Can two people with achondroplasia have a child without it? ›

If both parents have achondroplasia there is a 50 percent chance to have a child with achondroplasia, a 25 percent chance that the child will not inherit the gene and be of average height, and a 25 percent chance that the child will inherit one abnormal gene from each parent, which can lead to severe skeletal problems ...

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What is the new drug for achondroplasia? ›

Vosoritide is considered a milestone in treating dwarfism associated with achondroplasia: a genetic disorder in which mutation occurs in the fibroblast growth factor receptor 3 (FGFR3) gene responsible for converting cartilage into bones especially in the long bones of the arms and legs.

Does achondroplasia affect the brain? ›

Neurologic Problems in Achondroplasia. Neurological impairment is caused by compression created as children grow faster than their bones. Arrested bone growth at the base of the skull and the spine can cause the spinal cord and brain stem to become compressed.

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Where is achondroplasia most common in the world? ›

Based on the meta‐analysis, the worldwide birth prevalence of achondroplasia was estimated to be 4.6 per 100,000. Substantial regional variation was observed with a considerably higher birth prevalence reported in North Africa and the Middle East compared to other regions, particularly Europe and the Americas.

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What is the difference between achondroplasia and dwarfism? ›

Achondroplasia is a bone growth disorder that causes disproportionate dwarfism. Dwarfism is defined as a condition of short stature as an adult. People with achondroplasia are short in stature with a normal sized torso and short limbs. It's the most common type of disproportionate dwarfism.

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Should people with dwarfism have kids? ›

Dwarfism is not a disease that requires a "cure." Just like their average-height peers, people with dwarfism go to college, drive cars, find meaningful jobs, get married, and have children.

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Can you be a carrier of achondroplasia? ›

Around 80% of individuals with achondroplasia have parents of normal height and are born with a new gene alteration (de novo mutation). It is rare that these parents will have another child with achondroplasia. Only one parent needs to pass down the gene for a child to be born with achondroplasia (autosomal dominant).

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What is the current term for dwarfism? ›

The terms "little person", "LP" and "person of short stature" are the preferred terms of those with this disorder, and while many are uncomfortable with "dwarf" it remains a common term in some areas.

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What is the difference between dwarfism and a midget? ›

A: In some circles, a midget is the term used for a proportionate dwarf. However, the term has fallen into disfavor and is considered offensive by most people of short stature.

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What is the life expectancy of someone with achondroplasia? ›

Disease Overview

Achondroplasia does not typically cause impairment or deficiencies in mental abilities. If the bones that join the head and neck do not compress the brainstem or upper spinal cord (craniocervical junction compression), life expectancy is near normal.

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What is the rarest form of dwarfism? ›

Primordial dwarfism is a specific type of severe proportionate dwarfism, in which individuals are small for their chronological age from the very beginning of life. Microcephalic osteodysplastic primordial dwarfism type I (MOPD I) is the rarest type.

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Achondroplasia - A Bibliography and Dictionary for Physicians, Patients, and Genome Researchers - PDF Free Download (2024)

FAQs

Is achondroplasia the same as dwarfism? ›

Does achondroplasia affect the brain? ›