Robert Nussbaum - Thompson & Thompson Genetics in Medicine

Eighth Edition

Robert L. Nussbaum, MD, FACP, FACMG

Holly Smith Chair of Medicine and Science

Professor of Medicine, Neurology, Pediatrics and Pathology

Department of Medicine and Institute for Human Genetics

University of California San Francisco

San Francisco, California

Roderick R. McInnes, CM, MD, PhD, FRS(C), FCAHS, FCCMG

Alva Chair in Human Genetics

Canada Research Chair in Neurogenetics

Professor of Human Genetics and Biochemistry

Director, Lady Davis Institute

Jewish General Hospital

McGill University

Montreal, Quebec, Canada

Huntington F. Willard, PhD

President and Director

The Marine Biological Laboratory

Woods Hole, Massachusetts

and

Professor of Human Genetics

University of Chicago

Chicago, Illinois

With Clinical Case Studies updated by:

Ada Hamosh, MD, MPH

Professor of Pediatrics

McKusick-Nathans Institute of Genetic Medicine

Scientific Director, OMIM

Johns Hopkins University School of Medicine

Baltimore, Maryland

1600 John F. Kennedy Blvd.

Ste 1800

Philadelphia, PA 19103-2899

THOMPSON & THOMPSON GENETICS IN MEDICINE, EIGHTH EDITIONISBN: 978-1-4377-0696-3

Copyright 2016 by Elsevier Inc. All rights reserved.

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Notices

Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary.

Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility.

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Previous editions copyrighted 2007, 2004, 2001, 1991, 1986, 1980, 1973, 1966.

Library of Congress Cataloging-in-Publication Data

Nussbaum, Robert L., 1950- , author.

Thompson & Thompson genetics in medicine / Robert L. Nussbaum, Roderick R. McInnes, Huntington F. Willard.Eighth edition.

p. ; cm.

Genetics in medicine

Thompson and Thompson genetics in medicine

Includes bibliographical references and index.

ISBN 978-1-4377-0696-3 (alk. paper)

I. McInnes, Roderick R., author. II. Willard, Huntington F., author. III. Title. IV. Title: Genetics in medicine. V. Title: Thompson and Thompson genetics in medicine.

[DNLM: 1. Genetics, Medical. QZ 50]

RB155

616.042dc23

2015009828

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Printed in Canada.

Last digit is the print number: 9 8 7 6 5 4 3 2 1

In their preface to the first edition of Genetics in Medicine, published nearly 50 years ago, James and Margaret Thompson wrote:

Genetics is fundamental to the basic sciences of preclinical medical education and has important applications to clinical medicine, public health and medical research. This book has been written to introduce the medical student to the principles of genetics as they apply to medicine, and to give him (her) a background for his own reading of the extensive and rapidly growing literature in the field. If his (her) senior colleagues also find it useful, we shall be doubly satisfied.

What was true then is even more so now as our knowledge of genetics and of the human genome is rapidly becoming an integral part of public health and the practice of medicine. This new edition of Genetics in Medicine, the eighth, seeks to fulfill the goals of the previous seven by providing an accurate exposition of the fundamental principles of human and medical genetics and genomics. Using illustrative examples drawn from medicine, we continue to emphasize the genes and mechanisms operating in human diseases.

Much has changed, however, since the last edition of this book. The rapid pace of progress stemming from the Human Genome Project provides us with a refined catalogue of all human genes, their sequence, and an extensive, and still growing, database of human variation around the globe and its relationship to disease. Genomic information has stimulated the creation of powerful new tools that are changing human genetics research and medical genetics practice. Throughout, we have continued to expand the scope of the book to incorporate the concepts of personalized health care and precision medicine into Genetics in Medicine by providing more examples of how genomics is being used to identify the contributions made by genetic variation to disease susceptibility and treatment outcomes.

The book is not intended to be a compendium of genetic diseases nor is it an encyclopedic treatise on human genetics and genomics in general. Rather, the authors hope that the eighth edition of Genetics in Medicine will provide students with a framework for understanding the field of medical genetics and genomics while giving them a basis on which to establish a program of continuing education in this area. The Clinical Casesfirst introduced in the sixth edition to demonstrate and reinforce general principles of disease inheritance, pathogenesis, diagnosis, management, and counselingcontinue to be an important feature of the book. We have expanded the set of cases to add more common complex disorders to the set of cases. To enhance further the teaching value of the Clinical Cases, we continue to provide a case number (highlighted in green) throughout the text to direct readers to the case in the Clinical Case Studies section that is relevant to the concepts being discussed at that point in the text.