Emery and Rimoin’s principles and practice of medical genetics and genomics. Clinical principles and applications

414 Pages·2019·19.241 MB·English

by  Grody, Wayne W., Korf, Bruce R., Pyeritz, Reed E.

EMERY AND RIMOIN’S
PRINCIPLES AND PRACTICE
OF MEDICAL GENETICS AND
GENOMICS
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EMERY AND RIMOIN’S
PRINCIPLES AND PRACTICE
OF MEDICAL GENETICS AND
GENOMICS
Clinical Principles and Applications
Seventh Edition
Edited by
Reed E. Pyeritz
Perelman School of Medicine at the University of Pennsylvania,
Philadelphia, PA, United States
Bruce R. Korf
University of Alabama at Birmingham, Birmingham, AL, United States
Wayne W. Grody
UCLA School of Medicine, Los Angeles, CA, United States
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C O N T E N T S
List of Contributors ix 3.9 Cytogenomic Copy Number
Preface to the Seventh Edition of Emery and Rimoin’s Abnormalities 65
Principles and Practice of Medical Genetics and 3.10 X-Linked ID 66
Genomics xi 3.11 Fragile X Syndrome 69
Preface to Clinical Principles and Applications xiii 3.12 Autism Spectrum Disorders 69
3.13 Inborn Errors of Metabolism and
1 A Clinical Approach to the Dysmorphic Child 1
ID 70
Kenneth L. Jones and Marilyn C. Jones
3.14 CNS Malformations, Intellectual
1.1 Introduction 1
Disability and Brain Imaging 72
1.2 Prenatal Versus Postnatal Onset of
3.15 Summary 75
Developmental Problems 1
References 75
1.3 Prenatal-Onset Problems in
Further Reading 78
Development 4
1.4 Postnatal-Onset Problems in 4 Abnormal Body Size and Proportion 81
Development 12 Deepika D’Cunha Burkardt and John M. Graham Jr.
1.5 Conclusion 13 Glossary 81
References 13 4.1 Introduction 81
4.2 Approach to the Patient With Abnormal
2 Clinical Teratology 15
Stature 82
Sura Alwan and Jan M. Friedman
4.3 Mechanisms of Growth 84
2.1 Introduction 15
4.4 Pathologic Short Stature 100
2.2 Evaluating the Patient and Her
4.5 Pathologic Overgrowth 118
Exposure 21
4.6 Conclusion 129
2.3 Recognized Teratogenic Exposures 25
References 129
2.4 Paternal Exposures and Maternal Exposures
Further Reading 142
Before or Shortly After Conception 46
2.5 Future Perspective 46 5 Cytogenetic Analysis 145
2.6 Conclusion 46 Nancy B. Spinner and Malcolm A. Ferguson-Smith
References 47 5.1 Introduction 145
Further Reading 60 5.2 Milestones in Human Cytogenetics 145
5.3 Indications for Cytogenetic Analysis 148
3 Neurodevelopmental Disabilities: Global
5.4 Tissue Samples and Cell Culture 149
Developmental Delay, Intellectual Disability, and
5.5 Chromosome Banding 149
Autism 61
5.6 Normal Human Karyotype 149
John B. Moeschler
5.7 Chromosome Abnormalities 152
3.1 Intellectual Disability and Global
5.8 In Situ Hybridization 152
Developmental Delay 61
Acknowledgments 162
3.2 Global Developmental Delay 61
References 162
3.3 Definition of a Diagnosis 62
Further Reading 164
3.4 Whole Exome Sequencing 63
3.5 Whole Genome Sequencing 64 6 Diagnostic Molecular Genetics 165
3.6 Phenotyping 64 Wayne W. Grody and Joshua L. Deignan
3.7 Genetic Mechanisms of ID 65 6.1 Introduction 165
3.8 Diagnostic Testing of Patients With ID of 6.2 Indications for Molecular Genetic
Unknown Cause 65 Testing 166
v
vi CONTENTS
6.3 Technical Approaches to Molecular 9.3 The Process of Genetic Consultation
Genetic Testing 169 for Common, Chronic Diseases of
6.4 Molecular Genetic Diagnosis of Some Adulthood 268
Commonly Tested Diseases 174 9.4 Genetic Healthcare Models 277
6.5 Mitochondrial DNA Disorders 189 9.5 Summary 278
6.6 Other Targets of Molecular Genetic References 278
Screening 189
10 Carrier Screening and Heterozygote Testing 283
6.7 Pharmacogenetic Testing 190
Matthew J. McGinniss and Molly A. McGinniss
6.8 Quality Assurance, Reimbursement, and
Glossary 283
Regulatory Issues 191
10.1 Introduction 283
6.9 Internet Resources for Molecular
10.2 Carrier Screening in Clinical
Genetic Testing 193
Practice 284
6.10 Societal Impact of the New Genetic
10.3 Carrier Screening in Individuals of
Technology 194
Defined Subpopulation Groups 285
6.11 Future Directions 195
10.4 Therapeutic Implications for
References 196
Heterozygotes 292
7 Therapies for Lysosomal Storage Diseases 205 10.5 Sensitivity and Specificity 292
Robert J. Desnick, Kenneth H. Astrin and 10.6 Cost and Feasibility 293
Edward H. Schuchman 10.7 Genetic Counseling and Informed
7.1 Introduction 205 Consent 293
7.2 Enzyme Replacement Therapy 205 10.8 Conclusions 294
7.3 Bone Marrow Transplantation 209 Acknowledgments 295
7.4 Substrate Reduction Therapy 210 References 295
7.5 Pharmacologic Chaperone Therapy 213
11 Circadian Rhythms and Disease 299
7.6 Emerging Therapies: Gene Therapy and
Shirley L. Zhang and Amita Sehgal
Genome Editing 217
11.1 Introduction 299
References 220
11.2 Molecular Mechanisms 299
8 Transplantation Genetics 229 11.3 Central and Peripheral Clocks 300
Daniel Graziano and Massimo Trucco 11.4 Circadian Diseases 300
8.1 The Major Histocompatibility 11.5 Metabolic and Cardiovascular
Complex 229 Disorders 302
8.2 Historical Iter Toward Histocompatibility 11.6 Cancer 304
Definition 234 11.7 Psychologic and Neurologic Diseases
8.3 Currently Most Used Methods for HLA and Circadian Rhythms 304
Typing 244 11.8 Chronotherapy 306
8.4 Clinical Significance of HLA Molecular 11.9 Concluding Remarks 307
Typing 249 References 307
8.5 Stem Cells and Transplantation 253
12 The Genomic Health Record: Current Status and
8.6 Concluding Remarks 255
Vision for the Future 315
References 258
Marc S. Williams
9 Genetic Evaluation for Common, Chronic 12.1 Introduction 315
Disorders of Adulthood 265 12.2 Conclusion 323
Maren T. Scheuner and Shweta U. Dhar References 323
9.1 Background 265 Further Reading 325
9.2 Outcomes of Genetic Services 265
CONTENTS vii
13 Ethical and Social Issues in Clinical 15 Implementation of Genomic Medicine: An
Genetics 327 International Perspective 369
Rachel Irving and Angus John Clarke Angeliki Panagiotara, Efthymios Skoufas, Constantina
13.1 Introduction 327 Chalikiopoulou, Evangelia-Eirini Tsermpini, Marina
13.2 The Historical Context 328 Bartsakoulia, Theodora Katsila and George P. Patrinos
13.3 Genetic Counseling, Testing, and 15.1 Introduction 369
Screening 328 15.2 Large-Scale Genomic Medicine
13.4 Diagnostic Genetic Testing 331 Initiatives 370
13.5 Predictive Genetic Testing 334 15.3 National Genomic Medicine
13.6 Confidentiality 335 Initiatives 370
13.7 Genetic Testing in Childhood 336 15.4 Large-Scale Regional Genome
13.8 Population Genetic Screening 338 Initiatives 375
13.9 Other Challenges in Genetic 15.5 Corporate Genomic Medicine
Counseling 345 Initiatives 376
Acknowledgments 352 15.6 Studying Founder Populations 377
References 352 15.7 Conclusions and Future
Perspectives 377
14 Genetics and Genomics in Public Health 355
15.8 Competing Interests 378
Debra Lochner Doyle and Muin J. Khoury
References 378
14.1 What Is Public Health Genetics/
Further Reading 380
Genomics? 355
14.2 The Purposes of Public Health 356 Index 381
14.3 The Public Health System
Infrastructure 358
14.4 Evolution and Convergence of Two
Fields of Science—Public Health and
Genetics/Genomics 360
14.5 Future Direction for Public Health
Genetics/Genomics 363
References 365
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L I S T O F C O N T R I B U TO R S
Sura Alwan Malcolm A. Ferguson-Smith
Department of Medical Genetics, University of British Cambridge Resource Centre for Comparative
Columbia, Vancouver, BC, Canada Genomics, Department of Veterinary Medicine,
University of Cambridge, Cambridge, United Kingdom
Angus John Clarke
Institute of Medical Genetics, University Hospital of Jan M. Friedman
Wales, Heath Park, Cardiff, Wales, United Kingdom; Department of Medical Genetics, University of British
Institute of Medical Genetics, School of Medicine, Columbia, Vancouver, BC, Canada
Heath Park, Cardiff, Wales, United Kingdom
John M. Graham Jr.
Kenneth H. Astrin Consultant in Clinical Genetics and Dysmorphology,
Department of Genetics and Genomic Sciences, Mount Cedars-Sinai Medical Center, Los Angeles, CA,
Sinai School of Medicine, New York, NY, United States; United States; Consultant in Clinical Genetics and
Department of Preclinical Sciences, New York College Dysmorphology, Harbor-UCLA Medical Center,
of Podiatric Medicine, New York, NY, United States Torrance, CA, United States; Professor Emeritus of
Pediatrics, David Geffen School of Medicine at UCLA,
Marina Bartsakoulia
Los Angeles, CA, United States
University of Patras School of Health Sciences,
Department of Pharmacy, Patras, Greece Daniel Graziano
Tissue Typing Laboratory, Allegheny Health Network,
Deepika D’Cunha Burkardt
Allegheny General Hospital, Pittsburgh, PA, United
Medical Genetics Resident, Center for Human
States
Genetics, University Hospitals/Case Western Reserve
University, Cleveland, OH, United States Wayne W. Grody
UCLA School of Medicine, Los Angeles, CA, United
Constantina Chalikiopoulou
States
University of Patras School of Health Sciences,
Department of Pharmacy, Patras, Greece Rachel Irving
Institute of Medical Genetics, University Hospital of
Joshua L. Deignan
Wales, Heath Park, Cardiff, Wales, United Kingdom
Departments of Pathology and Laboratory Medicine,
David Geffen School of Medicine at UCLA, University Kenneth L. Jones
of California, Los Angeles, CA, United States Department of Pediatrics, University of California, San
Diego, CA, United States; Rady Children’s Hospital, San
Robert J. Desnick
Diego, CA, United States
Department of Genetics and Genomic Sciences, Mount
Sinai School of Medicine, New York, NY, United States Marilyn C. Jones
Department of Pediatrics, University of California, San
Shweta U. Dhar
Diego, CA, United States; Rady Children’s Hospital, San
Department of Molecular & Human Genetics, Baylor
Diego, CA, United States
College of Medicine, Houston, TX, United States
Theodora Katsila
Debra Lochner Doyle
University of Patras School of Health Sciences,
Washington State Department of Health Screening and
Department of Pharmacy, Patras, Greece
Genetics, Kent, WA, United States
ix