LIMITED OFFER
Save 50% on book bundles
Immediately download your ebook while waiting for your print delivery. No promo code is needed.
Book sale: Save up to 25% on print and eBooks. No promo code needed.
Save up to 25% on print and eBooks.
Emery and Rimoin's Principles and Practice of Medical Genetics
6th Edition - March 20, 2013
Editors: David L. Rimoin, Reed E. Pyeritz, Bruce Korf
eBook ISBN:
9 7 8 - 0 - 1 2 - 3 8 3 8 3 5 - 3
For decades, Emery and Rimoin’s Principles and Practice of Medical Genetics has provided the ultimate source for practicing clinicians to learn how the study of genetics can be… Read more
Purchase Options
For decades, Emery and Rimoin’s Principles and Practice of Medical Genetics has provided the ultimate source for practicing clinicians to learn how the study of genetics can be integrated into practice.
With almost 5,000 pages of detailed coverage, this fully online sixth edition of the classic reference adds the latest information on prenatal diagnosis, genetic screening, genetic counseling, and treatment strategies to complete its coverage of the growing field for medical students, residents and physicians involved in the care of patients with genetic conditions. Clinically oriented information is supported by expanded sections on basic principles of genetics, research approaches, and analytics to embrace the evolving population of students, researchers, and practitioners who are integrating their work to provide advanced diagnosis, prevention and treatment of human disease.
With advances in high-throughput technologies propelling the closer integration of lab and clinical work, this edition bridges the gap between high-level molecular genetics and clinical application.
- Features 174 review-length contributions that encompass traditional and new areas of the field - including in cancer genetics, genomic technologies, and molecular assays
- Provides many thousands of pertinent literature references guiding the reader in identifying related topics
- Fully illustrated with hundreds of color images, supporting identification, concept illustration and method processing
Medical and research libraries and institutions serving researchers of human genetics/genomics; cancer, neuroscience, metabolic, endocrinology, pharmacology, behaviour, immunology, hematology, orthopaedic, pediatric, gene therapy researchers; advanced students, specialists, and medical practitioners across medical disciplines as well systems biology, molecular medicine, and genetic epidemiology.
Preface
Foreword
Personal Memories of David Rimoin
Basic Principles
Chapter 1. History of Medical Genetics
1.1 Preface (Peter Harper)
1.2 Introduction
1.3 Foundations of Medical Genetics Before 1956
1.4 Growth and Development of Medical Genetics: 1956 to the Present
1.5 The Future
1.6 Addendum (PSH)
1.7 A Timeline for Medical Genetics
References
Further Reading
Chapter 2. Medicine in a Genetic Context
2.1 Introduction
2.2 The Principles of Disease
2.3 Defining Disease
2.4 The How Questions
2.6 The Why Questions
2.7 Prevention and Treatment
2.8 Conclusion
References
Chapter 3. Nature and Frequency of Genetic Disease
3.1 Introduction
3.2 Frequency of Genetic Disease
3.2.2 Single-Gene Disorders
3.2.3 Multifactorial Disorders
3.2.4 Somatic Cell Genetic Disorders
3.3 Morbidity and Mortality Due to Genetic Disease
References
Chapter 4. Genomics and Proteomics
4.1 Genes and Human Disease
4.2 Genomics
4.3 Mapping the Human Genome
4.4 Sequencing the Human Genome
4.5 Current Apporaches to Sequence Parts or the Whole Human Genome
4.6 An Approach for Cloning Human Disease Genes
4.7 Sequence-Based Methods for Detecting Chromosomal Abnormalities
4.8 Proteomics
Glossary
References
Chapter 5. Genome and Gene Structure
5.1 Introduction
5.2 Double Helix Structure, DNA Replication, Transcription, and Meiotic Recombination
5.3 Organization of Genomic DNA
5.4 Gene Structure and the Molecular Pathway of Gene Expression
References
Chapter 6. Epigenetics
6.1 Introduction
6.2 Epigenetic Mechanisms: Chromatin, DNA Methylation and Long Noncoding RNAs
6.3 Epigenetic Reprogramming
6.4 Epigenetic Regulation of X Inactivation
6.5 Genomic Imprinting
6.6 Genetic Disorders Due to Genes Affecting Chromatin Structure
6.7 Methods For Studying Epigenetic Marks
6.8 Cancer Epigenetics
6.9 Environmental Influences on Epigenetic Traits
6.10 Abnormalities in Epigenetic Programming Linked to Infertility and Assisted Reproduction
6.11 In Utero Epigenetic Programming of Adult Traits and Disease
6.12 Genetic–Epigenetic Interactions
6.13 The Future: Epigenomics
References
Websites
Chapter 7. Human Gene Mutation in Inherited Disease: Molecular Mechanisms and Clinical Consequences
7.1 Introduction
7.2 Molecular Mechanisms of Mutation Causing Human Inherited Disease
7.3 Disease-Causing Mutations
7.4 Consequences of Mutations
7.5 General Principles of Genotype–Phenotype Correlations
7.6 Why Study Mutation?
Acknowledgments
References
Further Reading
Chapter 8. Genes in Families
8.1 Introduction
8.2 Pedigree Construction
8.3 Unifactorial Inheritance/Single-Gene Disorders
8.4 Dominance and Recessiveness
8.5 Autosomal-Dominant Inheritance
8.6 Autosomal Recessive Inheritance
8.7 Sex-Linked Inheritance
8.8 X-Linked Recessive Inheritance
8.9 X-Linked Dominant Inheritance
8.10 Y-Linked (Holandric) Inheritance
8.11 Partial Sex Linkage
Cross References
References
Chapter 9. Analysis of Genetic Linkage
9.1 Introduction to Linkage Analysis
9.2 Linkage Analysis: Basic Concepts
9.3 Extending Parametric Linkage Analysis
9.4 Linkage Analysis for Complex and Quantitative Traits
9.5 Linkage Analysis: Future Directions
Web pages for Linkage Analysis Software are listed in Tables 9-1 and 9-2.
Additional Web Pages
Further Reading
Chapter 10. Chromosomal Basis of Inheritance
10.1 Introduction
10.2 Chromosome Structure
10.3 Chromosomes in Cell Division
10.4 Methods for Studying Human Chromosomes
10.5 Functional Organization of Chromosomes
10.6 Sex Chromosomes and Sex Determination
10.7 Uniparental Disomy and Imprinting
10.8 Chromosome Abnormalities
10.9 Concluding Remarks
Glossary
References
Chapter 11. Mitochondrial Medicine: The Mitochondrial Biology and Genetics of Metabolic and Degenerative Diseases, Cancer, and Aging
Abbreviations
11.1 Mitochondrial Biology and Genetics
11.2 Inherited nDNA Mitochondrial Diseases
11.3 Mitochondrial Etiology for Common Metabolic and Visceral Diseases
11.4 Mitochondrial Etiology for Neurodegenerative Diseases
11.5 Mitochondrial Defects in Cancer
11.6 Therapeutic Approaches to Mitochondrial Disease
11.7 A Mitochondrial Paradigm for Complex Disease
Acknowledgments
Cross References
References
Websites Cited
Further Reading
Chapter 12. Multifactorial Inheritance and Complex Diseases
12.1 Introduction
12.2 Definitions and Terminology
12.3 Determining the Genetic Component of a Trait
12.4 The International HapMap Project
12.5 Genome-Wide Association Studies
12.6 Association Methods/Statistical Analysis
12.7 Analysis of Rare Variants Using New Technologies
12.8 Integration of Genetic, Genomic, and Functional Data for Analysis of Multifactorial Diseases
12.9 Conclusions
References
Chapter 13. Population Genetics
13.1 Introduction
13.2 Hardy–Weinberg Law
13.3 Factors That Affect Hardy–Weinberg Equilibrium
13.4 Applications in Population Genetics
References
Relevant Websites
Further Reading
Chapter 14. Pathogenetics of Disease
14.1 Introduction
14.2 The Scope of Abnormal Phenotypes: Disease and Malformation
14.3 Physiologic Homeostasis
14.4 Multivariate Normal Distributions and the Threshold Model
14.5 Ontogenesis of Anatomic Structures: Angular Homeostasis
14.6 Pathogenetics of Refined Traits
14.7 Pathways and Multiple-Stage Processes
14.8 Molecular Pathogenetics
14.9 Conclusions
Acknowledgments
Cross References
References
Chapter 15. Human Developmental Genetics
15.1 Introduction and Overview
15.2 Timing of Normal Human Development
15.3 The Concept of Developmental Fields and Field Defects
15.4 Cellular Signaling in Development: The Concepts of Induction and Competence
15.5 A Limited Repertoire of Developmental Genes and Pathways
15.6 Steps and Concepts in Embryonic Development
15.7 Regulation of Gene Expression in Development
15.8 Developmental Gene Pathways and Families
15.9 Organogenesis
15.10 Conclusion
References
Chapter 16. Twins and Twinning
16.1 Introduction
16.2 Determining Zygosity
16.3 Incidence of Twins
16.4 Vanishing Twin
16.5 Structural Defects in Twins
16.6 Twins in Genetic Studies
16.7 Dizygotic Twins
16.8 Monozygotic Twins
16.9 Conclusions
Permissions
Cross References
References
Chapter 17. The Molecular Biology of Cancer
17.1 Introduction
17.2 A Genetic Basis of Cancer
17.3 Viral Oncogenes
17.4 Oncogenic Alleles in Human Cancers
17.5 Tumor Suppressor Genes
17.6 The Role of DNA Damage Repair Genes in Inherited Cancer Syndromes
References
Chapter 18. The Biological Basis of Aging: Implications for Medical Genetics
18.1 Introduction
18.2 What is Aging?
18.3 Why do we Age?
18.4 How do we Age?
18.5 Progeroid Syndromes of Humans
18.5.3 Human Allelic Variants Homologous to Pro-Longevity Genes in Model Organisms
References
Chapter 19. Pharmacogenetics and Pharmacogenomics
19.1 Introduction
19.2 Fundamental Aspects of Clinical Pharmacology
19.3 Classical Genetics and Pharmacogenetics: 1900 to Approximately 1990
19.4 Ethnic Differences in Gene–Drug Interactions
19.5 Pharmacogenomics
19.6 Conclusions
Acknowledgments
References
Further Reading
General Principles
Chapter 20. Genetic Evaluation for Common Diseases of Adulthood
20.1 Background
20.2 The Process of Genetic Evaluation for Common Diseases
20.3 Integrating Genetic Information into Routine Clinical Practice
20.4 Summary
References
Chapter 21. Genetic Counseling and Clinical Risk Assessment
21.1 What Is Genetic Counseling?
21.2 Process of Genetic Counseling
21.3 Adult-Onset Disorders
21.4 Genetic Risk Assessment and Calculation in the Clinical Setting
Acknowledgments
Cross References
References
Further Reading
Chapter 22. Cytogenetic Analysis
22.1 Introduction
22.2 Milestones in Human Cytogenetics
22.3 The Indications for Cytogenetic Analysis
22.4 Tissue Samples and Cell Culture
22.5 Chromosome Banding
22.6 The Normal Human Karyotype
22.7 Chromosome Abnormalities
22.8 In situ Hybridization
Acknowledgments
Cross References
References
Further Reading
Chapter 23. Diagnostic Molecular Genetics
23.1 Introduction
23.2 Indications for Molecular Genetic Testing
23.3 Technical Approaches to Molecular Genetic Testing
23.4 Molecular Genetic Diagnosis of Particular Diseases
23.5 Mitochondrial DNA Disorders
23.6 Other Targets of Molecular Genetic Screening
23.7 Pharmacogenetic Testing
23.8 Quality Assurance, Reimbursement, and Regulatory Issues
23.9 Internet Resources for Molecular Genetic Testing
23.10 Societal Impact of the New Genetic Technology
References
Chapter 24. Heterozygote Testing and Carrier Screening
24.1 Introduction
24.2 Carrier Screening in Clinical Practice
24.3 Carrier Screening in Individuals of Defined Subpopulation Groups
24.4 Therapeutic Implications for Heterozygotes
24.5 Methods and Tissues Used in Carrier Identification
24.6 Problems in Heterozygote Detection
24.7 Sensitivity and Specificity
24.8 Cost and Feasibility
24.9 Age for Carrier Testing
24.10 Conclusions
Acknowledgments
References
Chapter 25. Prenatal Screening for Neural Tube Defects and Aneuploidy
25.1 Introduction
25.2 Neural Tube Defects
25.3 Aneuploidy
25.4 Summary
References
Chapter 26. Techniques for Prenatal Diagnosis
26.1 Introduction
26.2 Amniocentesis
26.3 Chorionic Villus Sampling
26.4 Fetal Blood Sampling
26.5 Fetal Tissue Sampling
26.6 Coelocentesis
26.7 Embryoscopy
26.8 Polar Body Biopsy
26.9 Preimplantation Genetic Diagnosis
26.10 Ultrasonography
26.11 Fetal Cells and Fetal DNA in Maternal Blood
26.12 Future Directions
References
Chapter 27. Neonatal Screening
27.1 Introduction
27.2 Historical Aspects
27.3 Components of Screening Programs
27.4 Potential Problems in Newborn Screening
27.5 Disorders and Conditions Detected by Newborn Blood Screening
27.6 Other Newborn Screening
27.7 Issues and Concerns in Screening
Cross References
Glossary
References
Web Resources
Further Reading
Chapter 28. Therapies for Lysosomal Storage Diseases
28.1 Introduction
28.2 ERT for Lysosomal Storage Diseases
28.3 Substrate Reduction Therapy
28.4 Pharmacologic Chaperone Therapy
28.5 Conclusions and Future Directions
Acknowledgments
Cross-References
References
Relevant Websites
Chapter 29. Gene Therapy: From Theoretical Potential to Clinical Implementation
29.1 Genes as Medicines—The Origins of Gene Therapy
29.2 The Basic Science: Gene Transfer (Tables 29-1–29-3)
29.3 Developing Cell-Type-Specific and Regulatable Gene Delivery Vectors
29.4 The Clinical Science: Toward Gene Therapy of Human Disease
29.5 CODA
Cross References
References
Chapter 30. Ethical and Social Issues in Clinical Genetics
30.1 Introduction
30.2 The Historical Context
30.3 Genetic Counseling, Testing and Screening
30.4 Goals and Outcomes of Genetic Services
30.5 Nondirectiveness in Genetic Counseling
30.6 Diagnostic Genetic Testing
30.7 Predictive Genetic Testing
30.8 Confidentiality
30.9 Genetic Testing in Childhood
30.10 Population Genetic Screening
30.11 Newborn Screening
30.12 Antenatal Screening
30.13 Carrier Screening
30.14 Other Challenges in Genetic Counseling
30.15 Research in Human Genetics
30.16 Genetics, Geneticization and Society
30.17 Reproductive Technologies and Cloning: “Reprogenetics”
Acknowledgments
Further Reading
References
Websites
Chapter 31. Legal Issues in Genetic Medicine
31.1 Introduction
31.2 Genetic Malpractice and the Duty to Warn
31.3 Genetic Counseling
31.4 Abortion
31.5 Adoption
31.6 Surrogacy
31.7 Frozen Embryos
31.8 Newborn Screening
31.9 Prenatal and Carrier Screening
31.10 Genetic Discrimination
31.11 Regulation of Genetic Diagnostic Tests
31.12 Direct to Consumer Genetic Testing
31.13 Regulation of Human Genetic Research
31.14 Regulation of Research with Stem Cells Derived from Human Embryos
31.15 Genes and Patents
31.16 The Orphan Drug Act
31.17 Conclusion
Cross-references (Suggestions)
References
Further Reading
Relevant Websites
Applications to Clinical Problems
Chapter 32. Genetics of Female Infertility in Humans
32.1 The Hypothalamic–Pituitary–Gonadal Axis
32.2 The Diagnosis of Hypogonadism
32.3 Categories of Hypogonadism
32.4 Eugonadal Infertility
32.5 Specific Disorders in Each Diagnostic Category
32.6 Hypogonadotropic Hypogonadism
32.7 Hypergonadotropic Hypogonadism
References
Chapter 33. Genetics of Male Infertility
33.1 Male Infertility—Introduction
33.2 Chromosome Anomalies
33.3 Gene defects Involved in Endocrine Forms of Infertility
33.4 Monogenic Defects in Post-testicular and Primary Testicular Forms of Male Infertility
33.5 Syndromic Monogenic Defects
33.6 Conclusion
References
Chapter 34. Fetal Loss
34.1 Background
34.2 Definition of Terms
34.3 Early Pregnancy Loss
34.4 Late Pregnancy Loss
34.5 Evaluation and Management of Recurrent Abortion
34.6 Conclusions
Cross References
References
Relevant Web sites
Chapter 35. A Clinical Approach to the Dysmorphic Child
35.1 Introduction
35.2 Prenatal Versus Postnatal Onset of Developmental Problems
35.3 Prenatal-Onset Problems in Development
35.4 Postnatal-Onset Problems in Development
35.5 Conclusion
References
Chapter 36. Clinical Teratology
36.1 Introduction
36.2 Evaluating the Patient and Her Exposure
36.3 Recognized Teratogenic Exposures
36.4 Paternal Exposures and Maternal Exposures before or Shortly after Conception
36.5 Conclusion
References
Chapter 37. Neurodevelopmental Disabilities: Global Developmental Delay, Intellectual Disability, and Autism
37.1 Intellectual Disability and Global Developmental Delay
37.2 Global Developmental Delay
37.3 Definition of a Diagnosis
37.4 Genetic Mechanisms of ID
37.5 Diagnostic Testing of Patients with ID of Unknown Cause
37.6 Summary
References
Chapter 38. Abnormal Body Size and Proportion
38.1 Introduction
38.2 Pathologic Short Stature
38.3 Pathologic Overgrowth
Acknowledgments
References
Relevant Web Pages
Chapter 39. Susceptibility and Response to Infection
39.1 Introduction
39.2 Heterozygous Advantage and Homozygous Disadvantage
39.3 Genome-Wide Association Studies And Human Infection
39.4 Cell Surface Proteins
39.5 Intracellular Proteins
39.6 Extracellular Proteins
39.7 Conclusion
References
Chapter 40. Transplantation Genetics
Abbreviations
40.1 Introduction
40.2 The Physiologic Function of MHC Molecules
40.3 The Structure of Human Histocompatibility Molecules
40.4 The Chromosomal Organization of the HLA Complex
40.5 Minor Histocompatibility Systems
40.6 Serologic Methods for HLA Typing
40.7 Cellular Methods for HLA Typing
40.8 Molecular Methods for HLA Typing
40.9 Clinical Significance of HLA Molecular Typing
40.10 Genetics of Xenotransplantation
40.11 Stem Cells and Transplantation
40.12 Conclusion
Acknowledgments
References
List of Useful Websites
Chapter 41. The Genetics of Disorders Affecting the Premature Newborn
41.1 Introduction
41.2 Respiratory Distress Syndrome
41.3 Bronchopulmonary Dysplasia
41.4 Patent Ductus Arteriosus
41.5 Intraventricular Hemorrhage
41.6 Retinopathy of Prematurity
41.7 Necrotizing Enterocolitis
References
Chapter 42. Disorders of DNA Repair and Metabolism
42.1 Mendelian Pattern of Inheritance
42.2 Disorders of Nucleotide Excision Repair: Xeroderma Pigmentosum and Cockayne Syndrome
42.3 Disorders of Base Excision Repair: MUTYH and Colon Cancer Risk
42.4 Disorders of Mismatch Repair: Lynch Syndrome and Turcot Syndrome
42.5 Disorders Associated With Double Strand Break Recognition and Repair: Ataxia-Telangiectasia and Related Conditions
42.6 Crosslink Repair and Homologous Recombination Defects: Breast–Ovarian Cancer and Fanconi Anemia
42.7 Disorders Associated with Recq Helicase Deficiency: Bloom, Werner, and Rothmund–Thomson Syndromes
42.8 Gene–Environment Interactions: Gorlin–Goltz Syndrome
References
Applications to Specific Disorders
Pathways
Chapter 43. Autosomal Trisomies
43.1 Introduction
43.2 Genetic Counseling in the Trisomies
43.3 Down Syndrome (Trisomy 21)
43.4 Trisomy 18
43.5 Trisomy 13
References
Chapter 44. Sex-Chromosome Abnormalities
44.1 Introduction
44.2 The Epidemiology of Sex-Chromosome Abnormalities
44.3 Turner Syndrome
44.4 Klinefelter Syndrome
44.5 47,XXX Syndrome
44.6 X Chromosome Mosaicism
44.7 Sex Chromosome Tetrasomy and Pentasomy (Polysomy)
44.8 47,XYY Karyotype
44.9 Structural Abnormalities of the Y Chromosome
44.10 Prenatal Diagnosis of Sex Chromosome Abnormalities
References
Further Reading
Cross References
Chapter 45. Deletions and Other Structural Abnormalities of the Autosomes
45.1 Introduction
45.2 Translocations
45.3 Uniparental Disomy
45.4 Deletion
45.5 Duplication
Cross References
References
Chromosomal Disorders
Chapter 46. Congenital Heart Defects
46.1 Introduction
46.2 The Evaluation of the Patient with Congenital Heart Defect
46.3 Specific Syndromes with Congenital Heart Defect
46.4 Chromosomal Disorders
46.5 Microdeletions/Microduplication Syndromes
46.6 Single-Gene Disorders
46.7 Holt–Oram syndrome
46.8 CHARGE Syndrome
46.9 Zellweger Syndrome
46.10 Smith–Lemli–Opitz Syndrome
46.11 Maternal Diabetes
46.12 Maternal Cigarette Smoking
46.13 Maternal Drug Ingestion
46.14 Folic Acid Supplementation
46.15 Empirical Risks for Sibs of Children with Isolated Heart Defects
46.16 Empirical Risks for Offspring
Appendix
References
Websites
Chapter 47. Inherited Cardiomyopathies
47.1 Introduction
47.2 Hypertrophic Cardiomyopathy
47.3 Dilated Cardiomyopathy
47.4 Atypical Cardiomyopathies
47.5 Conclusion
Cross References
References
Further Reading
Relevant Websites
Chapter 48. Heritable and Idiopathic Forms of Pulmonary Arterial Hypertension
48.1 Historical Perspectives and Introduction
48.2 Nomenclature
48.3 Incidence and Prevalence of HPAH and IPAH
48.4 Phenotype and Natural History of HPAH and IPAH
48.5 Inheritance and Genetics of PAH in Families
48.6 Connecting BMPR2 to PAH
48.7 Molecular and Cellular Pathogenesis
48.8 Diagnosis
48.9 Management
48.10 Counseling
Acknowledgments
Abbreviations
References
Further Reading
Relevant Websites
Chapter 49. Hereditary Hemorrhagic Telangiectasia (Osler–Weber–Rendu Syndrome)
49.1 Introduction
49.2 Phenotype and Natural History
49.3 Etiology
49.4 Pathogenesis
49.5 Diagnosis
49.6 Management
Acknowledgments
References
Chapter 50. Hereditary Disorders of the Lymphatic System and Varicose Veins
50.1 Development of the Lymphatic System
50.2 Disorders of the Lymphatic System
50.3 Mendelian Disorders Affecting both the Lymphatic and Venous System
50.4 Varicose Veins
50.5 Genetic Counseling
References
Webpages
Cross References
Chapter 51. The Genetics of Cardiac Electrophysiology in Humans
51.1 Introduction
51.2 Specific Cardiac Dysrhythmias
51.3 Primary Abnormalities in Cardiac Rhythm: Ventricular Tachydysrhythmias
51.4 Primary Abnormalities in Cardiac Rhythm: Supraventricular Dysrhythmias
51.5 Primary Conduction Abnormalities
51.6 Familial Dysrhythmias Associated with Myocardial Disease
51.7 Neurologic Disorders Associated with Dysrhythmias and Conduction Disease
51.8 Congenital Heart Disease and Dysrhythmias or Conduction Disease
51.9 Summary
References
Further Reading
Chapter 52. Genetics of Blood Pressure Regulation
52.1 Introduction
52.2 Mendelian Forms of Hypertension
52.3 Candidate Genes
52.4 Genome-wide Association Studies
Acknowledgment
References
Chapter 53. Preeclampsia
53.1 Introduction
53.2 Classification
53.3 Pathologic and Molecular Basis
53.4 Genetic Basis of Preeclampsia
53.5 Animal Models
References
Relevant Web Pages
Chapter 54. Common Genetic Determinants of Coagulation and Fibrinolysis
54.1 Introduction
54.2 Genetic Variants Influencing Components of the Coagulation Cascade
54.3 Genetic Variants Influencing Natural Anticoagulants
54.4 Genetic Variants Influencing Components of the Fibrinolytic Cascade
54.5 Genetic Variants Influencing Platelet Function
54.6 Genome-Wide Association Analysis for Thrombosis
54.7 How do we Account for the Missing Heritability?
54.8 Impact of Genetic Risk Factors on the Clinical Management of Thrombosis
Cross References
References
Chapter 55. Genetics of Atherosclerotic Cardiovascular Disease
Abbreviations
55.1 Introduction
55.2 Challenges to Genetic Studies of CHD
55.3 Mouse Models of Atherosclerosis
55.4 Candidate Gene Studies in Humans
55.5 Genome Wide Association Studies
55.6 GWAS Findings for CVD Risk Factors
55.7 Genetic Risk Scores and Prediction Algorithms for Personalized Medicine
55.8 Summary and Future Directions
Cross References
References
Further Reading
Chapter 56. Disorders of the Venous System
56.1 Introduction
56.2 The Venous System
56.3 Disorders of the Venous System
56.4 Conclusion
Acknowledgments
References
Relevant Websites
Chapter 57. Capillary Malformation/Arteriovenous Malformation
57.1 Introduction
57.2 Capillary Malformation
57.3 Sturge–Weber Syndrome
57.4 Capillary Malformation–arteriovenous Malformation
57.5 Cerebral Cavernous Malformation
Acknowledgments
Cross References
References
Relevant Websites
Cardiovascular Disorders
Chapter 58. Cystic Fibrosis
Abbreviation list
58.1 Incidence of Cystic Fibrosis
58.2 Clinical Features
58.3 Genetics
58.4 Diagnosis and Differential Diagnosis
58.5 Management
Acknowledgments
References
Chapter 59. Genetic Underpinnings of Asthma and Related Traits
Glossary
Nomenclature
59.1 Introduction
59.2 The Genetics of Asthma and Allergic Diseases
59.3 Conclusion
Acknowledgments
Cross References
References
Relevant web pages
Chapter 60. Hereditary Pulmonary Emphysema
Abbreviations
60.1 Introduction
60.2 Diseases with Airflow Limitation: Definitions
60.3 Phenotypic Evaluation in COPD
60.4 Cigarette Smoking and COPD
60.5 Severe AAT Deficiency
60.6 Risk of COPD in Z Allele Heterozygotes
60.7 COPD and COPD-Related Phenotypes in Other Genetic Syndromes
60.8 Risk to Relatives for Non-AAT COPD
60.9 Segregation Analysis
60.10 Linkage Analysis
60.11 Genetic Association Studies
60.12 Animal Models of COPD
60.13 Conclusions
Acknowledgment
References
Relevant Websites
Chapter 61. Interstitial and Restrictive Pulmonary Disorders
61.1 Introduction
61.2 Idiopathic Interstitial Pneumonia and Familial Interstitial Pneumonia
61.3 Associated Polymorphisms in Other Common Forms of ILD
61.4 Genetic Syndromes with ILD Manifestations
References
Respiratory Disorders
Chapter 62. Congenital Anomalies of the Kidney and Urinary Tract
Glossary
62.1 Introduction
62.2 Clinical Features
62.3 Genetics
62.4 Errors of Organogenesis
62.5 Errors of Migration and Position
62.6 Errors Resulting in Obstruction
Cross References
References
Relevant Webpages
Further Reading
Chapter 63. Cystic Diseases of the Kidney
63.1 Introduction
63.2 Autosomal Dominant Polycystic Kidney Disease (MIM 173900)
63.3 Autosomal Recessive Polycystic Kidney Disease (MIM 263200)
63.4 Familial Nephronophthisis
63.5 Medullary Cystic Kidney Disease
63.6 Multicystic Dysplastic Kidney Disease (MKD)
63.7 Genetic Syndromes with Cystic Renal Disease as a Major Component
63.8 Mechanisms of Cystogenesis
Cross References
References
Further Reading
Relevant Web Pages
Chapter 64. Nephrotic Disorders
64.1 Introduction
64.2 Glomerular Filtration Barrier
64.3 Nephrin Gene (NPHS1) Mutations
64.4 Podocin Gene (NPHS2) Mutations
64.5 Wilms Tumor Suppressor Gene (WT1) Mutations
64.6 Phospholipase Cε1 Gene (PLCE1) Mutations
64.7 Laminin-β2 Gene (LAMB2) Mutations
64.8 Transient Receptor Potential C6 Ion Channel Gene (TRPC6) Mutations
64.9 CD2-Associated Protein Gene (CD2AP) Mutations
64.10 Alpha-Actinin-4 Gene (ACTN4) Mutations
64.11 NS Caused by Inverted Formin 2 Gene (INF2) Mutations
64.12 Other Genetic Forms of NS
64.13 Diagnosis of NS
64.14 Management of NS Patients
64.15 Conclusions
References
List of Relevant Websites
Cross Reference
Chapter 65. Renal Tubular Disorders
65.1 Introduction
65.2 Generalized Disorders of Tubular Function (Fanconi Syndrome)
65.3 Disorders of Amino Acid Transport
65.4 Renal Tubular Acidosis
65.5 Disorders of Sugar Transport
65.6 Hypophosphatemic Rickets
65.7 Conclusion
References
Further Reading
Cross References
Chapter 66. Cancer of the Kidney and Urogenital Tract
Abbreviations
66.1 Tumors of the Kidney
66.2 Bladder Neoplasms
66.3 Carcinoma of the Prostate
66.4 Testicular Neoplasms
References
Cross References
Renal Disorders
Chapter 67. Gastrointestinal Tract and Hepatobiliary Duct System
Abbreviation
67.1 Introduction
67.2 Embryological Background
67.3 Classification of Gastrointestinal Disorders
References
Relevant Web Pages
Chapter 68. Inflammatory Bowel Disease
Abbreviation
68.1 Introduction and Disease Definition
68.2 Phenotypic Heterogeneity
68.3 Racial and Ethnic Differences
68.4 Familial Aggregation
68.5 Twin and Spouse Studies
68.6 Inferences Regarding Mode of Inheritance
68.7 Association of IBD With Rare Genetic Syndromes
68.8 Associations with Other Diseases
68.9 Gene and Environmental Interactions
68.10 Gene Identification
68.11 Candidate Gene Studies
68.12 Clinical Application of Genetic Information
References
Further Reading
Chapter 69. Bile Pigment Metabolism and Its Disorders
69.1 Introduction
69.2 Formation of Bilirubin
69.3 Structure of Bilirubin
69.4 Possible Physiologic Benefits of Biliverdin and Bilirubin
69.5 Toxic Effects of Bilirubin
69.6 Disposition of Bilirubin
69.7 Bilirubin Measurement
69.8 Bilirubin in Body Fluids
69.9 Disorders of Bilirubin Metabolism
Acknowledgments
References
Chapter 70. Cancer of the Colon and Gastrointestinal Tract
70.1 Introduction
70.2 The Genetics of Colorectal Cancer
70.3 Familial Colorectal Cancer
70.4 Other Familial Gastrointestinal Polyposis Syndromes
70.5 Genetics of Gastric Cancer
References
Gastrointestinal Disorders
Chapter 71. Hemoglobinopathies and Thalassemias
71.1 Introduction
71.2 Normal Human Hemoglobin
71.3 Hemoglobin Biosynthesis
71.4 Human Hemoglobin Variants
71.5 Sickle-cell Anemia and Related Disorders
71.6 Unstable Hemoglobin Variants
71.7 Hemoglobin Variants with Altered Oxygen Affinity
71.8 M Hemoglobin Variants
71.9 Thalassemias
References
Chapter 72. Other Hereditary Red Blood Cell Disorders
72.1 Hemolysis due to Hereditary Red Blood Cell Enzyme Disorders
72.2 Purine and Pyrimidine Abnormalities Associated with Hemolysis
72.3 Hemolysis due to Hereditary Red Blood Cell Membrane Disorders
72.4 Megaloblastic Anemias
72.5 Dyserythropoietic Anemias
72.6 Sideroblastic Anemias
72.7 Methemoglobinemia
References
Chapter 73. Hemophilias and Other Disorders of Hemostasis
73.1 Overview of Hemostasis and Thrombosis
73.2 The Coagulation Cascade
73.3 Inherited Disorders Predisposing to Thrombosis
References
Chapter 74. Rhesus and Other Fetomaternal Incompatibilities
74.1 Historical Background of Rh Alloimmunization
74.2 Etiology of Alloimmunization
74.3 Detection of Fetomaternal Hemorrhage
74.4 Rh Blood Group System
74.5 Alloimmune Thrombocytopenia
74.6 Management of Alloimmunization
References
Further Reading
Chapter 75. Leukemias, Lymphomas, and Other Related Disorders
75.1 Introduction
75.2 General Patterns of Chromosome Aberrations and Genomic Abnormalities in Leukemia and Lymphoma
75.3 Significance of Detecting Acquired Chromosome and Gene Abnormalities in Leukemia and Lymphoma
75.4 Application of Cytogenetic, Fish, and Microarray Techniques in Diagnosis of Leukemia and Lymphoma
75.5 Myeloproliferative Neoplasm
75.6 Myelodysplastic Syndromes
75.7 Acute Myeloid Leukemia de Novo
75.8 AML and MDS Associated with Prior Cytotoxic Treatment
75.9 B-Cell Acute Lymphoblastic Leukemia
75.10 Recurring Chromosome and Genomic Abnormalities in T-Cell ALL
75.11 Leukemia in Children with Down Syndrome
75.12 PreNatal Origins of Childhood Leukemia
75.13 Non-Hodgkin Lymphomas
75.14 Molecular Analysis of Recurrent Chromosome Abnormalities
Cross References
References
Chapter 76. Immunologic Disorders: Autoimmunity: Genetics and Immunologic Mechanisms
76.1 Introduction
76.2 The Immune Response
76.3 Autoimmune Pathology
76.4 Autoreactive T Cells and the Failure of Tolerance
76.5 Genetics of Autoimmune Diseases
76.6 HLA Allelic Diversity and Population Genetics
76.7 Genetic Susceptibility to Autoimmune Disease
References
Chapter 77. Systemic Lupus Erythematosus
77.1 Introduction
77.2 Historical Background, Definition, and Classification
77.3 Pathogenic Autoantibodies and Immune Complexes
77.4 The Genetics of Human SLE
77.5 Gene Expression Patterns Associated with SLE
77.6 Pregnancy Counseling of SLE Patients
77.7 Concluding Remarks
Cross Reference
References
Further Reading
Chapter 78. Rheumatoid Disease and Other Inflammatory Arthropathies
Glossary
78.1 Introduction
78.2 Rheumatoid Arthritis
78.3 Seronegative Spondyloarthropathies
78.4 Juvenile Idiopathic Arthritis
References
Chapter 79. Amyloidosis and Other Protein Deposition Diseases
79.1 Introduction
79.2 Hereditary Systemic Amyloidosis
79.3 Hereditary Localized Amyloidosis
79.4 Hereditary Non-Amyloid Protein Deposition Disease
79.5 Conclusion
References
Chapter 80. Immunodeficiency Disorders
80.1 Introduction
80.2 Specific Inherited Immunodeficiency Disorders
80.3 Primary B-cell Deficiencies (Humoral Immune Defects)
80.4 Immunodeficiencies with Immune Dysregulation
80.5 Immunodeficiency Syndromes
80.6 Conclusion
References
Chapter 81. Inherited Complement Deficiencies
81.1 Overview
81.2 Introduction to the Complement System
81.3 The Classical Pathway
81.4 The Alternative Pathway
81.5 The Lectin Activation Pathway
81.6 The Membrane Attack Complex
81.7 Regulation of Complement Activation
81.8 Inherited Complement Deficiencies
81.9 Management of Complement Deficiencies
References
Further Reading
Hematologic Disorders
Chapter 82. Disorders of Leukocyte Function
82.1 Introduction
82.2 Historical Background
82.3 Phagocyte Development, Kinetics, and Functions
82.4 Granulocyte Function Disorders
82.5 Monocytes/Macrophages Function Disorders
Cross References
References
Chapter 83. Genetic Disorders of the Pituitary Gland
83.1 Introduction
83.2 Anterior Pituitary
83.3 Posterior Pituitary: Genetic Disorders of AVP Deficiency
83.4 Genetic Testing
References
Chapter 84. Thyroid Disorders
84.1 Introduction
84.2 Congenital Hypothyroidism
84.3 Genetic Hyperthyroidism
84.4 Thyroid Disease Associated with Chromosomal Abnormalities and Contiguous Gene Deletion Syndromes
84.5 Genetic Basis of Autoimmune Thyroid Disease
84.6 Genetic Basis of Thyroid Carcinoma
References
Chapter 85. Parathyroid Disorders
85.1 Calcium Homeostasis
85.2 Primary Hyperparathyroidism
85.3 Familial Hypocalciuric Hypercalcemia
85.4 Neonatal Severe Hyperparathyroidism
85.5 CASR Mutations in Familial Hypocalciuric Hypercalcemia and Neonatal Severe Hyperparathyroidism
85.6 Mucolipidosis and Neonatal Hyperparathyroidism
85.7 Multiple Endocrine Neoplasia
85.8 Multiple Endocrine Neoplasia Type 1
85.9 Multiple Endocrine Neoplasia Type 2
85.10 Multiple Endocrine Neoplasia Type 4
85.11 Hyperparathyroidism-Jaw Tumor Syndrome
85.12 Other Hereditary Hyperparathyroidism
85.13 Diagnosis and Differential Diagnosis of Hypercalcemia
85.14 Jansen Metaphyseal Chondrodysplasia (Pseudohyperparathyroidism)
85.15 Primary Hypoparathyroidism
85.16 Familial Isolated Hypoparathyroidism
85.17 Hypoparathyroidism with Multiple Malformations
85.18 Hypoparathyroidism Due to Metabolic Disease
85.19 Autoimmune Hypoparathyroidism: Acquired and Inherited Disorders
85.20 Pseudohypoparathyroidism
85.21 Other Phenotypes Associated with GNAS Mutations
85.22 The Parathyroid Hormone Receptor and Skeletal Dysplasias
85.23 NHERF1 Mutations and Renal Responsiveness to Parathyroid Hormone
85.24 Hypomagnesemia
85.25 Management of Hypoparathyroidism
Cross References
References
Websites
Chapter 86. Diabetes Mellitus
86.1 Introduction
86.2 Difficulties in Genetic Studies of Diabetes
86.3 Diabetes in Families and Twins
86.4 Genetic Heterogeneity in Diabetes
86.5 Type 2 Diabetes Mellitus
86.6 Final Considerations and Speculations
Cross References
References
Further Reading
Relevant Web Pages
Chapter 87. Genetic Disorders of the Adrenal Gland
87.1 Clinical Aspects: Normal and Abnormal Adrenal Function
87.2 Steroid 21-Hydroxylase Deficiency
87.3 Steroid 11β-Hydroxylase Deficiency
87.4 3β-Hydroxysteroid Dehydrogenase Deficiency
87.5 Steroid 17α-Hydroxylase/17,20-Lyase Deficiency
87.6 Congenital Lipoid Adrenal Hyperplasia
87.7 Treatment
87.8 Congenital Adrenal Hyperplasia: Prenatal Diagnosis and Treatment
Acknowledgment
References
Further Reading
Chapter 88. Disorders of the Gonads, Genital Tract, and Genitalia
88.1 Introduction
88.2 46,XX Disorders of Sexual Development
References
Further reading
Chapter 89. Cancer of the Breast and Female Reproductive Tract
89.1 Historical Background: Mapping Breast Cancer Genes
89.2 Discovery of BRCA1
89.3 Discovery of BRCA2
89.4 Pathology of Familial Breast Cancers
89.5 BRCA1 and BRCA2 Mutation Analysis
89.6 Rare Familial Syndromes Associated with Increased Risk for Breast or Ovarian Cancer
89.7 Low-Penetrance Breast Cancer Genes
89.8 Association Studies and Genomics of Breast Cancer
89.9 Hereditary Nonpolyposis Colorectal Cancer Syndrome (or Lynch Syndrome)
89.10 Endometrial Cancer
89.11 Familial Ovarian Cancer
89.12 Cervical Cancer
89.13 Implications of Familial Breast and Ovarian Cancers for Clinical Practice
89.14 Impact of Definitive Genetic Diagnosis on Clinical Practice
References
Endocrinologic Disorders
Chapter 90. Disorders of the Body Mass
90.1 Overview
90.2 Genetic Architecture of Obesity
90.3 Mendelian Disorders Associated with Increased BMI in Humans
References
Chapter 91. Genetic Lipodystrophies
91.1 Introduction
91.2 Mechanisms of Insulin Resistance and its Complications in Lipodystrophies
91.3 Genetic Lipodystrophies
91.4 Long-Term Complications
91.5 Treatment Options
References
Chapter 92. Amino Acid Metabolism
92.1 Disorders of Phenylalanine Metabolism
92.2 Disorders of Tyrosine Metabolism
92.3 Disorders of Glycine Metabolism
92.4 Disorders of Sulfur-Containing Amino Acids
92.5 Disorders of the BCAAs
92.6 Disorders of Proline and Hydroxyproline
92.7 Disorders of the Urea Cycle and Ornithine
92.8 Disorders of Serine Metabolism
92.9 Disorders of Amino Acids without Known Clinical Consequences
References
Further Reading
Chapter 93. Disorders of Carbohydrate Metabolism
93.1 Introduction
93.2 Disaccharidase Deficiencies
93.3 Glucose–Galactose Malabsorption
93.4 Disorders of Galactose Metabolism
93.5 Disorders of Fructose Metabolism
93.6 Disorders of Pentose Metabolism
93.7 Glycogen Storage Diseases
93.8 GSDs Primarily Involving the Liver
93.9 Other Liver Glycogenoses
93.10 GSD Primarily Involving Muscle
93.11 GSD Primarily with Cardiac Involvement
93.12 Gluconeogenic Disorders Associated with Lactic Acidosis
Acknowledgments
Cross References
References
Chapter 94. Congenital Disorders of Protein Glycosylation
94.1 Normal Protein Glycosylation
94.2 Congenital Disorders of Protein N-Glycosylation
94.3 Congenital Disorders of Protein O-Glycosylation
94.4 Congenital Disorders of Protein N- and O-Glycosylation
94.5 Perspectives
Cross References
References
Further Reading
Chapter 95. Purine and Pyrimidine Metabolism
Glossary
95.1 Introduction
95.2 Purine Metabolism
95.3 Pyrimidine Metabolism
Acknowledgments
Cross Reference
References
Further Reading
Chapter 96. Lipoprotein and Lipid Metabolism
Abbreviations
96.1 Introduction
96.2 Plasma Lipids, Lipoproteins And Apolipoproteins
96.3 Lipoprotein Metabolism
96.4 Monogenic Disorders of Lipoprotein Metabolism
96.5 Disorders with Primarily Elevated LDL Cholesterol
96.6 Disorders with Primarily Depressed LDL Cholesterol
96.7 Disorders with Primarily Elevated HDL Cholesterol
96.8 Disorders with Primarily Depressed HDL Cholesterol
96.9 Disorders with Primarily Elevated Triglycerides
96.10 Disorders with Multiple Lipoprotein Disturbances
96.11 Other Dyslipoproteinemias
96.12 General Priniciples in the Management of Dyslipidemia
96.13 Conclusion
References
Further reading
Relevant Web Pages
Chapter 97. Organic Acidemias and Disorders of Fatty Acid Oxidation
97.1 Organic Acidemias
97.2 Other Organic Acidemias
97.3 Disorders of Fatty Acid Oxidation: introduction
Cross References
References
Further Reading
Relevant Web Pages
Chapter 98. Vitamin D Metabolism or Action
98.1 History
98.2 Normal Physiology of Calciferols
98.3 5,6-cis-trans-isomerization
98.4 General Features of Calciferol Deficiency
98.5 Hereditary Vitamin D Dependency Type 1 (VDDR-1)-1-α-Hydroxylase Deficiency
98.6 Hereditary Vitamin D-Dependent Rickets Type 2 (VDDR-2)
98.7 States Resembling Hereditary Generalized Resistance to 1,25(OH)2D
98.8 Other Hereditary Defects in Calciferol Metabolism or Action
References
Further Reading
Chapter 99. Inherited Porphyrias
99.1 Introduction
99.2 The Heme Biosynthetic Pathway
99.3 Regulation of Heme Biosynthesis
99.4 Classification and Diagnosis of the Porphyrias
Acknowledgments
Chapters to Cross-Reference
Further Reading
Relevant Web Pages
Chapter 100. Inherited Disorders of Human Copper Metabolism
100.1 Introduction
100.2 Menkes Disease
100.3 Wilson Disease
Acknowledgments
References
Chapter 101. Iron Metabolism and Related Disorders
101.1 Introduction
101.2 Iron Balance and the Iron Cycle
101.3 Syndromes of Iron Overload
101.4 Other Disorders Resulting in Derangements of Iron Handling
References
Chapter 102. Mucopolysaccharidoses
102.1 General Aspects
102.2 Mucopolysaccharidosis I (IH Hurler, IS Scheie and IH/S Hurler–Scheie Disease)
102.3 Mucopolysaccharidosis II (Hunter Syndrome)
102.4 Mucopolysaccharidosis IIIA (Sanfilippo Syndrome, MPS IIIA)
102.5 Mucopolysaccharidosis IIIB (Sanfilippo Syndrome, MPS IIIB)
102.6 Mucopolysaccharidosis IIIC (Sanfilippo Syndrome, MPS IIIC)
102.7 Mucopolysaccharidosis IIID (Sanfilippo Syndrome, MPS IIID)
102.8 Mucopolysaccharidosis IVA and IVB (Morquio Syndrome, MPS IVA, MPS IVB)
102.9 Mucopolysaccharidosis V (Scheie Syndrome, MPS V)
102.10 Mucopolysaccharidosis VI (Maroteaux–Lamy Syndrome, MPS VI)
102.11 Mucopolysaccharidosis VII (Sly Syndrome, MPS VII)
102.12 Mucopolysaccharidosis VIII
102.13 Mucopolysaccharidosis IX (Natowicz Syndrome, MPS IX)
Appendix A Supplementary Data
References
Relavent Web Sites
Further Reading
Chapter 103. Oligosaccharidoses: Disorders Allied to the Oligosaccharidoses
103.1 Oligosaccharidoses
103.2 Disorders Allied to Oligosaccharidoses
Acknowledgments
References
Relevant Webpages
Chapter 104. Sphingolipid Disorders and the Neuronal Ceroid Lipofuscinoses or Batten Disease (Wolman Disease, Cholesteryl Ester Storage Disease, and Cerebrotendinous Xanthomatosis)
Glossary
104.1 Introduction
104.2 GM1-Gangliosidosis (β-Galactosidosis)
104.3 GM2-Gangliosidosis
104.4 Loss-of-Function Mutation of GM3-Synthase
104.5 Niemann–Pick Disease
104.6 Niemann–Pick Disease, Types A and B
104.7 Niemann–Pick Disease, Types C and D
104.8 Farber’s Disease
104.9 Acid Lipase Deficiency (Wolman Disease and Cholesteryl Ester Storage Disease)
104.10 Gaucher Disease
104.11 Galactosylceramide Lipidosis, Globoid Cell Leukodystrophy, or Krabbe Disease
104.12 Metachromatic Leukodystrophy
104.13 Fabry Disease
104.14 Neuronal Ceroid Lipofuscinosis or Batten Disease
104.15 Kufs Disease or Adult NCL
104.16 Congenital NCL/CNCL-CLN10/Cathepsin D or CTSD Deficiency
Acknowledgment
References
Chapter 105. Peroxisomal Disorders
Abbreviations
105.1 Introduction
105.2 Physiological Role of Peroxisomes
105.3 Additional Peroxisomal Functions
105.4 Biogenesis of Peroxisomes
105.5 Single Peroxisomal Enzyme Deficiencies
105.6 Rare Peroxisomal Disorders
Reference
Metabolic Disorders
Chapter 106. The Genetics of Personality
106.1 The Nature of Personality
106.2 Twin and Adoption Studies
106.3 The Search for Genes that Influence Personality
106.4 Strategies to Increase the Sensitivity of Genetic Studies of Personality
106.5 Gene–Environment Interplay and the Development of Personality
106.6 Conclusion
Cross References
References
Further Reading
Chapter 107. Fragile X Syndrome and X-linked Intellectual Disability
107.1 Overview
107.2 Fragile X Syndrome
107.3 Other Forms of XLID
107.4 Conclusion
Cross References
References
Further Reading
Chapter 108. Dyslexia and Related Communication Disorders
Abbreviations
108.1 Introduction
108.2 Definition
108.3 Primary Cognitive Deficit of Specific Reading Disability
108.4 Inheritance
108.5 Comorbidity
108.6 Recurrence Risks
108.7 Diagnosis and Differential Diagnosis
108.8 Treatment
References
Chapter 109. Attention-Deficit/Hyperactivity Disorder
109.1 Behavioral Genetics
109.2 Molecular Genetics
109.3 Conclusions
Cross References
References
Relevant Web Pages
Chapter 110. Autism Spectrum Disorders
110.1 Background
110.2 Diagnosis and Clinical Work Up
110.3 Medical Comorbidities
110.4 Etiology: Genes and the Environment
110.5 Pathophysiology
110.6 Syndromic Forms of ASD and Structural Chromosomal Variation
110.7 Linkage and Endophenotypes
110.8 Genome Wide Association Studies
110.9 Candidate Genes
110.10 Variable Expressivity and Variable Penetrance—Psychiatric Comorbidity and Disease Boundary Confusion
110.11 Conclusion
References
Chapter 111. Genetics of Alzheimer Disease
111.1 Background and History
111.2 Genetics of EOAD
111.3 Genetics of LOAD
References
Further Reading
Chapter 112. Schizophrenia and Affective Disorders
Glossary
112.1 Introduction
112.2 History and Definitions of the Disorders
112.3 Biology of the Disorders
112.4 Evidence Supporting a Genetic Component
112.5 Role of Genetics in Clinical Practice
112.6 Summary
Cross References
References
Further Reading and other sections refer to PPMG article template doc
Chapter 113. Addictive Disorders
113.1 Introduction
113.2 Genetic Aspects of Addiction
113.3 Gene Identification
113.4 Treatment of Addictions
113.5 Conclusion
References
Mental and Behavioral Disorders
Chapter 114. Neural Tube Defects
114.1 Embryology
114.2 Definition
114.3 Prevalence
114.4 Risk Factors
114.5 Diagnosis, Treatment, and Outcome
114.6 Prevention
114.7 Genetic Counseling
Acknowledgments
References
Further Reading
Chapter 115. Genetic Disorders of Cerebral Cortical Development
115.1 Introduction
115.2 Malformations Due to Abnormal Neuronal and Glial Proliferation or Apoptosis
115.3 Malformations Due to Abnormal Neuronal Migration
115.4 Malformations Due to Abnormal Cortical Organization
115.5 Malformations of Cortical Development, Not Otherwise Classified
115.6 Conclusions
Acknowledgments
Cross References
References
Further Reading
List of Relevant Web Pages
Chapter 116. Genetic Aspects of Human Epilepsy
Abbreviations
116.1 Introduction
116.2 Epilepsy: Definition
116.3 Epilepsy: Neurophysiological Basis
116.4 EEG in Epilepsy
116.5 Seizure Types, Epilepsy Syndromes
116.6 Genetic Studies in Human Epilepsy
116.7 Mechanistic Diversity in Genetic Epilepsy
116.8 Selected Genetic Epilepsy Syndromes
116.9 Clinical and Laboratory Evaluation
116.10 Genetic Counseling Issues in Epilepsy
116.11 Pharmacogenomics Issues in Epilepsy
116.12 Epilepsy and Pregnancy
116.14 Summary
Acknowledgments
Cross References
References
Relevant Webpages
Chapter 117. Basal Ganglia Disorders
117.1 Introduction
117.2 Diseases with Parkinsonism
117.3 Parkinson Disease
117.4 Parkinson Plus Syndromes
117.5 General Clinical Features of the Dystonias
117.6 Management and Treatment
117.7 Choreic Disorders
117.9 Clinical Features
Cross References
References
Further Reading
Chapter 118. The Hereditary Ataxias
118.1 Recessive Ataxias Caused by Catalytic Deficiencies
118.2 Intermittent Ataxias
118.3 Progressive Ataxias from Metabolic Insufficiency
118.4 Progressive Ataxias that are not Because of Metabolic Defects
118.5 Progressive Ataxias Associated with Defective DNA Repair Mechanisms
118.6 Other Recessive Progressive Ataxias
118.7 The Autosomal-Dominant Hereditary Ataxias
118.8 Episodic Ataxias
118.9 X-linked ataxias
118.10 Mitochondrial Ataxias
118.11 Conclusions
References
List of Relevant Web Pages
Chapter 119. Hereditary Spastic Paraplegia
119.1 Introduction
119.2 Maternal (Mitochondrial Genome) Inheritance
119.3 Association of HSP Gene Mutations with Syndromes Other than Spastic Paraparesis
119.4 Autosomal Dominant HSP
119.5 Autosomal Recessive HSP Genes
119.6 X-Linked HSP Genes
119.7 Emerging Concepts of HSP Pathogenesis
119.8 Animal Models of HSP
119.9 Conclusions
Cross-References
Acknowledgments
References
Chapter 120. Autonomic and Sensory Disorders
120.1 Introduction
120.2 Familial Dysautonomia
120.3 Congenital Sensory Neuropathy with Anhidrosis (HSAN Type IV)
References
Chapter 121. The Phakomatoses
121.1 Introduction
121.2 The Neurofibromatoses
Acknowledgments
References
Chapter 122. Multiple Sclerosis and Other Demyelinating Disorders
122.1 Introduction
122.2 Pediatric MS
122.3 Practical Applications of Genetic Studies
122.4 Krabbe Disease (Globoid Cell Leukodystrophy)
122.5 Metachromatic Leukodystrophy
122.6 X-Linked Adrenoleukodystrophy
References
Chapter 123. Genetics of Stroke
123.1 Introduction
123.2 Stroke Phenotypes
123.3 Heritability: Twin and Family Studies
123.4 Single-Gene Disorders Causing Stroke
123.5 CVT – Cerebral Venous Thrombosis (FVL, prothrombin)
123.6 Genome-Wide Association Studies and Genomics
123.7 Summary
Acknowledgment
References
Chapter 124. Primary Tumors of the Nervous System
Abbreviations
124.1 Introduction
124.2 Epidemiology
124.3 Classification
124.4 Inherited Tumor Syndromes Predisposing to Central Nervous System Tumors
124.5 Relative Risk of Cancer in First-Degree Relatives
124.6 Glial Tumors
124.7 Primitive Neuroectodermal Tumor and Medulloblastoma
124.8 Schwannoma (Neurilemmoma, Neurinoma)
124.9 Meningioma
Cross References
References
Relevant Webpages
Further Reading
Neurologic Disorders
Chapter 125. Muscular Dystrophies
Glossary
125.1 Introduction
125.2 Dystrophinopathies
125.3 Facioscapulohumeral Muscular Dystrophy
125.4 Emery–Dreifuss Muscular Dystrophies and Other Contractural Phenotypes
125.5 Limb-Girdle Muscular Dystrophies
125.6 Myofibrillar Myopathies and Other Distal Phenotypes
125.7 Congenital Muscular Dystrophies
125.8 Conclusions
References
List of relevant Relevant Web pages
Further Reading
Chapter 126. Hereditary Motor and Sensory Neuropathies
126.1 Introduction
126.2 Hereditary Motor and Sensory Neuropathies
126.3 Diseases Phenotypes
126.4 Distal Symmetric Polyneuropathy—Evidence-Based Medical Guidelines
126.5 Modes of Inheritance
126.6 Genetics
126.7 Charcot–Marie–Tooth “disease genes” Reveal a Cellular and Myelin Development/Maintenance Network
126.8 Genetic Counseling
126.9 Summary
Further Information
References
Chapter 127. Congenital (Structural) Myopathies
127.1 Introduction
127.2 Diagnosis
127.3 Management
127.4 Genetic Counseling
127.5 Nemaline (Rod) Myopathy
127.6 Myotubular (Centronuclear) Myopathies
127.6.7 Pathogenetic Considerations
127.7 The “Core Myopathies”: CCD and MmD
127.8 Congenital Fiber Type Disproportion
127.9 Myosin Storage (Hyaline Body) Myopathy
127.10 Myofibrillar Myopathies
Acknowledgments
References
Chapter 128. Spinal Muscular Atrophies
128.1 Introduction: Definition
128.2 Proximal Spinal Muscular Atrophy
128.3 Nonproximal Spinal Muscular Atrophy
128.4 Management
References
Chapter 129. Hereditary Muscle Channelopathies
129.1 Introduction
129.2 Electrophysiology of Clinical Weakness and Paralysis
129.3 Hereditary Channelopathies Affecting the End Plate
129.4 Hereditary Channelopathies Affecting the Plasmalemma
129.5 Hereditary Channelopathies of Excitation–Contraction Coupling
129.6 Critical Points in Functional and Genetic Studies
Acknowledgment
References
Relevant Web Pages
Chapter 130. Myotonic Dystrophies
130.1 Introduction
130.2 Clinical Features
130.4 Genetics
130.5 Molecular and Cell Biology
130.6 Genetic Counseling and Risk Estimation
130.7 Management
Cross References
References
Further Reading
Relevant Web Pages
Chapter 131. Hereditary and Autoimmune Myasthenias
131.1 Introduction
131.2 Normal Neuromuscular Transmission
131.3 Diagnostic Methods
131.4 Acetylcholine Receptor
131.5 Congenital Myasthenic Syndromes
131.6 Acquired Autoimmune Myasthenia Gravis
131.7 Immunogenetic Associations
131.8 Management
131.9 Lambert–Eaton Myasthenic Syndrome
References
Further Reading
Chapter 132. Motor Neuron Disease
132.1 Introduction
132.2 History
132.3 Epidemiology
132.4 Clinical Features
132.5 Clinical Variants of Amyotrophic Lateral Sclerosis
132.6 Pathology
132.7 Genetics of Familial Amyotrophic Lateral Sclerosis
132.8 Genetics of Sporadic Amyotrophic Lateral Sclerosis
132.9 Conclusion
References
Neuromuscular Disorders
Chapter 133. Color Vision Defects
133.1 Introduction
133.2 Photoreceptors
133.3 Molecular Biology of the Photopigments
133.4 Phototransduction
133.5 Genes Encoding the Photopigments
133.6 Color Vision Tests
133.7 The Molecular Basis of Variation in Normal Color Vision
133.8 The Molecular Basis of Color Vision Defects
133.9 The Genetics of Red–green Color Vision in Women
133.10 Blue–Yellow (Tritan) Color Vision Defects
133.11 The Achromatopsias
Acknowledgment
References
Websites
Further Reading
Chapter 134. Optic Atrophy
Glossary
134.1 Introduction
134.2 “Primary” Optic Atrophies
134.3 Complex Optic Atrophies
References
Chapter 135. Glaucoma
135.1 Introduction
135.2 Clinical Features of Heritable Forms of Glaucoma
135.3 Identification of Glaucoma Genes Using Linkage Analysis
135.4 Genes Causing Glaucoma in Animal Models
135.5 Identification of Glaucoma Genes Using Genomic Approaches
135.6 Conclusion
Cross References
References
Further Reading
Chapter 136. Defects of the Cornea
Glossary
136.1 Introduction
136.2 Dystrophies
136.3 Defects Associated with Systemic Disease
136.4 Other Inherited Corneal Abnormalities
136.5 Conclusion
References
Chapter 137. Congenital Cataracts and Genetic Anomalies of the Lens
Glossary
137.1 Introduction
137.2 Noncataractous Anomalies
137.3 Cataracts
137.4 Therapy
Acknowledgments
References
List of Relevant Web Pages
Chapter 138. Hereditary Retinal and Choroidal Dystrophies
138.1 Introduction
138.2 Inheritance Patterns and Molecular Genetics
138.3 Pigmentary Retinopathies/Retinitis Pigmentosa
138.4 Leber’s Congenital Amaurosis
138.5 The Primary Cone Degenerations
Cross References
References
Chapter 139. Strabismus
139.1 Introduction
139.2 Incidence and Pathophysiology
139.3 Clinical Background
139.4 Isolated Strabismus
139.5 Single Gene Defect Disorders
139.6 Strabismus Associated with Other Ocular Disease
139.7 Strabismus Associated with Multisystem Disease
139.8 Summary
References
Chapter 140. Retinoblastoma and the RB1 Cancer Syndrome
140.1 Introduction
140.2 Incidence and Prevalence
140.3 Theories of Tumorigenesis and RB1
140.4 The Natural History of Retinoblastoma Tumorigenesis
140.5 The RB1 Cancer Syndrome
140.6 Non-heritable (Somatic or Postzygotic) Retinoblastoma
140.7 Features of Retinoblastoma Common to Heritable and Non-heritable Cases
140.8 Clinical Genetics and Genetic Counseling
140.9 Approaches to Prenatal Assessment and Diagnosis
140.10 Conclusions
Cross References
References
Further Reading
Chapter 141. Anophthalmia, Microphthalmia, and Uveal Coloboma
Glossary
141.1 Introduction
141.2 Anophthalmia, Microphthalmia, and Uveal Coloboma
141.3 Genes and Syndromes Associated with Anophthalmia, Microphthalmia, and/or Uveal Coloboma
141.4 A Clinical Approach to the Patient with AMC
141.5 Persistence of the Fetal Vasculature/Persistent Hyperplastic Primary Vitreous
References
Further Reading
Relevant Websites
Ophthalmologic Disorders
Chapter 142. Hereditary Hearing Impairment
Glossary
Abbreviations
142.1 Introduction
142.2 Anatomy and Physiology
142.3 Prevalence and Classification of HL
142.4 Acquired Hearing Impairment
142.5 Teratogenic Hearing Impairment
142.6 Nonsyndromic Hereditary Hearing Impairment
142.7 Syndromic Hereditary Hearing Impairment
142.8 Inborn Metabolic Errors
142.9 Diagnosis and Differential Diagnosis
References
Further reading
Deafness
Chapter 143. Clefting, Dental, and Craniofacial Syndromes
143.1 Introduction
143.2 Development
143.3 Epidemiology
143.4 Genetics
143.5 Clinical Exam and Physical Findings
143.6 Conclusion
References
Chapter 144. Craniosynostosis
Glossary
144.1 Introduction
144.2 Skull and Sutural Development
144.3 Genetic Epidemiology of Craniosynostosis
144.4 Craniosynostosis Syndromes
144.5 Genes Responsible for Craniosynostosis
144.6 Other Syndromes with Craniosynostosis and their Genes
144.7 Non-syndromic Craniosynostoses and their Genes
144.8 Evaluation of Craniosynostosis
References
Craniofacial Disorders
Chapter 145. Abnormalities of Pigmentation
145.1 Introduction
145.2 The Pigmentary System
145.3 Genetics and Disorders of Human Pigmentation
145.4 Disorders of Melanosome Biogenesis/Transport—Hermansky–Pudlak Syndrome, Chédiak–Higashi Syndrome, and Griscelli Syndrome
145.5 Disorders of Melanocyte Survival—Vitiligo
Acknowledgment
References
Chapter 146. Ichthyosiform Dermatoses
146.1 Introduction
146.2 Approach to Diagnosis of Ichthyosis
146.3 The Morphology of Normal Skin
146.4 Ichthyosis Vulgaris
146.5 X-linked Ichthyosis
146.6 Autosomal Recessive Congenital Ichthyosis
146.7 Epidermolytic Hyperkeratosis
146.8 Ichthyosis of the Newborn
146.9 Hyperkeratosis of the Palms and Soles
146.10 Rare Ichthyoses
146.11 Phenotype by Function: Advances in Understanding
A List of Websites of Use to the Reader in Regard of the Topic
Cross Reference
References
Further Reading
Chapter 147. Epidermolysis Bullosa
Glossary
147.1 Introduction
147.2 Molecular Basis of Epidermal and Dermo-epidermal Adhesion
147.3 Classification
147.4 Clinical Features
147.5 Differential Diagnosis
147.6 Molecular Genetics of Epidermolysis Bullosa
147.7 Treatment and Therapeutics
147.8 Revertant Mosaicism
147.9 Animal Models
147.10 The Role of Patient Advocacy Organizations
Cross References
References
Further Reading
List of Websites Relavant to EB
Chapter 148. Ectodermal Dysplasias
Glossary
148.1 Introduction
148.2 Hypohidrotic Ectodermal Dysplasia
148.3 Odonto–Onycho–Dermal Dysplasia (OODD) Syndrome (MIM 257980)
148.4 P63-Related Ectodermal Dysplasia Syndromes
148.5 Ectrodactyly, Ectodermal Dysplasia, and Cleft Lip/Palate Syndrome (MIM 604292)
148.6 Ankyloblepharon, Ectodermal Defects, Cleft Lip/Palate (MIM 106260)
148.7 Rapp–Hodgkin Syndrome (MIM 129400)
148.8 Adult (Acro–Dermato–Ungual–Lacrimal–Tooth) Syndrome (MIM 103285)
148.9 Limb–Mammary Syndrome (MIM 603543)
148.10 Split Hand/Split Foot Malformation (SHFM4) (MIM 605289)
148.11 Hidrotic Ectodermal Dysplasia (Clouston Syndrome) (MIM 129500)
148.12 Tooth and Nail Syndrome (Witkop Syndrome)(MIM 189500)
148.13 IKBKG Gene-Related Disorders
Cross References
References
Relevant Web Pages
Further Reading
Chapter 149. Skin Cancer
149.1 Introduction
149.2 Basal Cell Carcinoma
149.3 Nevoid Basal Cell Carcinoma Syndrome (Gorlin–Goltz Syndrome)
149.4 Bazex–Dupre–Christol Syndrome
149.5 Squamous Cell Carcinoma
149.6 Xeroderma Pigmentosum
149.7 Multiple Self-healing Epitheliomas of Ferguson Smith
149.8 Epidermodysplasia Verruciformis
149.9 Recessive Dystrophic Epidermolysis Bullosa (of the Hallopeau–Siemens Type)
149.10 Porokeratoses
149.11 Muir–Torre Syndrome
149.12 Melanoma
Further Reading
Cross References
References
Chapter 150. Psoriasis
Glossary
150.1 Introduction
150.2 Clinical Features and Subtypes
150.3 Prevalence, Age at Onset and Sex Ratio
150.4 Genetic Epidemiology
150.5 Environmental Factors
150.6 Comorbidities
150.7 Histopathology and Lesional Evolution
150.8 Immunopathogenesis
150.9 Psoriasis Susceptibility Loci and their Roles in Disease Pathogenesis
150.10 Management
150.11 Conclusion
Cross References
References
Further Reading
Relevant Website
Chapter 151. Cutaneous Hamartoneoplastic Disorders
151.1 Introduction
151.2 Hereditary Leiomyomatosis and Renal-Cell Cancer
151.3 Birt–Hogg–Dubé Syndrome
References
Relevant Web pages
Chapter 152. Inherited Disorders of the Hair
Glossary
152.1 Introduction and Hair Anatomy
152.2 HF Morphogenesis and Cycling
152.3 The Hair Keratins and their Regulation
152.4 Desmosomes of the HF
152.5 Genetics of Hypotrichosis and Other Structural Hair Abnormalities
152.6 Hair Abnormalities in Association with Metabolic Diseases
152.7 Other Disorders Associated with Hair Phenotypes
152.8 Hypertrichosis
152.9 Genetics of Polygenic Diseases
Acknowledgments
References
Dermatologic Disorders
Chapter 153. Marfan Syndrome and Related Disorders
153.1 Introduction
153.2 Structure and Composition of Extracellular Microfibrils
153.3 Fibrillins
153.4 Functions of Microfibrils
153.5 Marfan Syndrome (OMIM ∗154700): The Prototype of Disorders of Microfibrilogenesis and the Fibrillins
153.6 Disorders Related to Marfan Syndrome through Phenotype, Etiology or Pathogenesis
Acknowledgments
References
Chapter 154. Ehlers–Danlos Syndrome
154.1 Introduction
154.2 Collagen Genes and Proteins
154.3 Biosynthesis of Collagens
154.4 Classical Ehlers–Danlos Syndrome (Types I and II—GRAVIS and Mitis)
154.5 Hypermobile Type (EDS Type III—Familial Hypermobility)
154.6 Vascular, Ecchymotic Type (EDS Type IV)
154.7 Kyphyoscoliotic Ehlers–Danlos Syndrome (EDS Type VI)
154.8 Arthrochalasis Types of Ehlers–Danlos Syndrome (EDS Types VIIA and VIIB)
154.9 Dermatosparaxis (EDS Type VIIC)
154.10 Other Forms of Ehlers–Danlos Syndrome
154.11 Summary
References
Chapter 155. Heritable Diseases Affecting the Elastic Fibers: Cutis Laxa, Pseudoxanthoma Elasticum, and Related Disorders
155.1 Introduction
155.2 Biology of Elastin
155.3 Elastin Deficiency Disorders
155.4 Elastin Accumulation Diseases
155.5 Disorders of Elastin Fibrillogenesis
Acknowledgments
References
Connective Tissue Disorders
Chapter 156. Osteogenesis Imperfecta (and Other Disorders of Bone Matrix)
Glossary
156.1 Introduction
156.2 Osteogenesis Imperfecta
156.3 Management of Osteogenesis Imperfecta
156.4 Clinical Features of the OI Syndromes
156.5 Other Manifestations of Osteogenesis Imperfecta
156.6 Syndromes with Osteoporosis and Eye Disease
156.7 Hypophosphatasia
156.8 Other Bone Fragility Disorders
References
Chapter 157. Disorders of Bone Density, Volume, and Mineralization
157.1 Introduction
157.2 Osteopetrosis Group of Disorders
157.3 Raine Dysplasia
157.4 Pyknodysostosis
157.5 Dysosteosclerosis
157.6 Osteopoikilosis, Buschke–Ollendorf Syndrome, and Melorheostosis
157.7 Osteopathia Striata
157.8 Craniotubular Remodeling Disorders
157.9 Craniotubular Remodeling Disorders Resulting From Mutations in Filamin a
157.10 Tubular Stenosis (Kenny–Caffey Syndrome)
157.11 Hyperphosphatasemia with Osteoectasia
157.12 Disorders of Parathyroid Hormone Resistance
157.13 X-linked Hypophosphatemic Rickets
References
Chapter 158. Chondrodysplasias
158.1 Introduction
158.2 Classification and Nomenclature
158.3 Clinical Evaluation
158.4 Radiologic Evaluation
158.5 Chondro-osseous Morphology
158.5 Biochemical and Molecular Abnormalities
158.6 Summary
References
Further Reading
Chapter 159. Abnormalities of Bone Structure
Glossary
159.1 Introduction
159.2 Dysplasia Epiphysealis Hemimelica
159.3 Hereditary Multiple Exostoses
159.4 Langer–Giedion Syndrome
159.5 Enchondromatosis
159.6 Maffucci Syndrome
159.7 Metachondromatosis
159.8 Fibrous Dysplasia of Bone
159.9 Cherubism
References
Relevant Websites
Chapter 160. The Dysostoses
160.1 Introduction
160.2 Dysostoses with Predominantly Axial Involvement
160.3 Predominant Limb Involvement
160.4 Predominant Limb Involvement with Other Associated Abnormalities
References
Further reading
Chapter 161. Arthrogryposes (Multiple Congenital Contractures)
161.1 Introduction
161.2 Approach
161.3 Differential Diagnosis
161.4 Frequently Observed Conditions
161.8 Summary
References
Relevant Websites
Chapter 162. Common Skeletal Deformities
162.1 Introduction
162.2 Idiopathic Scoliosis
162.3 Spondylolisthesis
162.4 Congenital Dislocation of the HIP
162.5 Clubfoot
162.6 Juvenile Osteochondroses
References
Relevant Website
Chapter 163. Hereditary Noninflammatory Arthropathies
163.1 Introduction
163.2 Spondyloepiphyseal Dysplasias
163.3 Familial Osteoarthropathy
163.4 Primary Osteoarthropathy of the Hip
163.5 Mseleni Joint Disease
Acknowledgments
References
Skeletal Disorders
Chapter 164. Pathways—Cohesinopathies
164.1 Introduction
164.2 Clinical Features of CdLS
164.3 Diagnosis
164.4 Genetics
164.5 Other Disorders of Cohesin and Sister Chromatid Cohesion
References
Chapter 165. Genes and Mechanisms in Human Ciliopathies
Glossary
165.1 Cilia Structure and Function
165.2 Clinical Aspects of Ciliopathies and Ciliopathy-Like Disorders
165.3 Clinical Aspects of Ciliopathies
165.4 Molecular and Developmental Mechanisms in Ciliopathies
165.5 Direct Interactions between Ciliopathy Proteins and Evidence for Complex Inheritance in a Subset of Families
Supplementary Data
Acknowledgments
References
Relevant Website
- No. of pages: 4700
- Language: English
- Published: March 20, 2013
- Imprint: Academic Press
- eBook ISBN: 9780123838353
DR
David L. Rimoin
Affiliations and expertise
Medical Genetics Institute, Los Angeles, CA, USARP
Reed E. Pyeritz
Dr. Reed Pyeritz is a medical genetics doctor in Philadelphia, Pennsylvania and is affiliated with Hospitals of the University of Pennsylvania-Penn Presbyterian. Dr. Pyeritz focuses his research in two areas – Mendelian disorders of the cardiovascular system (especially those involving defects of connective tissue) and ethical, legal and social implications of human genetics. He is continuing his studies, begun over 20 years ago, of Marfan syndrome and related conditions – diseases in which the aorta and occasionally major arterial branches gradually enlarge and dissect, leading to early demise if untreated. Current efforts include a multicenter trial of angiotensin receptor blockade in Marfan syndrome, the identification of additional genes that predispose to arteriopathy, and improving methods for diagnosing and treating arterio-venous malformations, especially in hereditary hemorrhagic telangiectasia (HHT). Dr. Pyeritz directs Penn CIGHT (Center for the Integration of Genetic Healthcare Technologies). Supported by the ELSI Branch of the National Human Genome Research Institute, Penn CIGHT conducts research in the broad area of ‘uncertainty’ as related to the introduction of evolving approaches to assaying a patient’s genotype.
Affiliations and expertise
William Smilow Professor of Medicine and Professor of Genetics, Senior Fellow, Leonard Davis Institute of Health Economics, Perelman School of Medicine, University of Pennsylvania, Smilow Center for Translational Research, Philadelphia, PA, USABK
Bruce Korf
Affiliations and expertise
University of Alabama at Birmingham, Birmingham, AL