Genetics of Ocular Diseases

Description

The book focuses on describing the importance of genetics in eye diseases in a comprehensive and concise manner. Mutations in different set of genes have been detected and incriminated in complex mechanisms of causing leading eye diseases such as cataract and glaucoma. This book written by well-established ophthalmologists and geneticists presents a complicated subject in simple and easy to understand manner. Chapters cover the concept of gene therapy which is an emerging subject with high potential. The book includes a separate chapter on genetic counseling, which has become an integral component of ophthalmology. The book will assist the practicing ophthalmologists in early diagnosis of genetic eye diseases as well as help the geneticists in understaning the basic concepts. It will also be useful for students who are preparing for MD, MS, DNB and FRCS examinations. Foreword Abstract Contents About the Editors 1: Genes and Genetics in Ophthalmology 1.1 Introduction 1.2 Gene Mapping 1.3 Human Genome Project 1.4 Next Generation Sequencing Technologies 1.5 Gene Therapy 1.6 Gene Editing References 2: Genetics in Corneal Dystrophy 2.1 Categorization of Corneal Dystrophy on Genetic Basis 2.2 Genetics in Corneal Dystrophy References 3: Genetics of Keratoconus 3.1 Introduction 3.2 Epidemiology 3.3 Evidence of Role of Genetics/Heredity 3.4 Environmental Risk Factors 3.5 Candidate Genes 3.6 Genome-Wide Studies 3.7 Linkage Studies in Families 3.8 Genome-Wide Association Studies 3.9 Combination of GWAS and Linkage Studies 3.10 Identity by Descent 3.11 Related Ocular and Systemic Diseases 3.12 Recent Research 3.13 Future Research References 4: Genetics of Dry Eye Disease 4.1 Definition and Classification 4.2 Molecular Mechanisms and Genetic Basis 4.3 Conclusions References 5: Genetics in Cataract: To Be or Not to Be 5.1 Embryology 5.2 Epidemiology 5.3 Techniques for Genetic Screening 5.4 Overview of Cataract Genetics 5.5 Genes Underlying Isolated or Primary Inherited Cataract 5.6 Cytoplasmic Cyrstallin Encoding Genes 5.7 Membrane Proteins Encoding Genes 5.8 Cytoskeletal Protein Encoding Genes 5.9 DNA- or RNA-Binding Proteins 5.10 Genes Associated with Age-Related Cataract 5.11 Conclusion References 6: Genetics of Congenital Glaucoma 6.1 Introduction 6.2 Primary Congenital Glaucoma (PCG) 6.2.1 Disease Overview and Definition 6.2.2 Epidemiology 6.2.3 Clinical Presentation 6.2.4 Examination Under Anesthesia 6.2.5 Pathophysiology of Primary Congenital Glaucoma 6.3 Genetic Architecture of Primary Congenital Glaucoma (PCG) 6.3.1 Pattern of Inheritance for PCG 6.3.2 Genetic Loci for Primary Congenital Glaucoma 6.3.3 PCG Related GLC3 Loci 6.3.4 Candidate Genes Identification for the PCG-Linked Loci 6.4 Cytochrome P4501B1 (CYP1B1)—“GLC3A” 6.4.1 CYP1B1 Protein and Expression 6.4.2 Structural Components of CYP1B1 6.4.3 CYP1B1 Mutational Landscape of PCG 6.4.4 Predominant PCG Associated CYP1B1 Mutations in Different Ethnic Populations 6.4.5 Genotype (CYP1B1 Mutations)–Phenotype (PCG) Correlations: A Complex Scenario 6.5 Genes for GLC3B and GLC3C Loci 6.6 Latent Transforming Growth Factor (TGF)-Beta Binding Protein 2 (LTBP2): Locus “GLC3D” 6.7 Tunica Interna Endothelial Cell Kinase (TEK): “GLC3E” Fifth Locus for PCG 6.8 Digenic Inheritance in PCG Associated Genes 6.9 Developmental Anomalies and Glaucoma 6.9.1 Axenfeld–Rieger Syndrome 6.9.2 Peters’ Anomaly 6.9.3 Aniridia 6.10 Evidence of Mitochondrial Mutations in PCG 6.11 Genetics Research and Testing Toward Molecular Diagnosis 6.12 Genetic Counseling 6.13 Understanding Glaucoma Through In Vitro and Animal Models 6.14 Summary References 7: Genetics in Glaucoma 7.1 Introduction 7.2 Genes Involved in the Development of the Eye 7.3 Discovering Candidate Genes for Glaucoma 7.4 How Genes Cause a Disorder? 7.5 Identification of Genes—Significance 7.6 Genetic Nomenclature 7.7 Primary Congenital Glaucoma (PCG) 7.8 Juvenile Onset Open Angle Glaucoma (JOAG) 7.9 Primary Open Angle Glaucoma (POAG) 7.10 Primary Angle Closure Glaucoma (PACG) 7.11 Developmental Glaucoma 7.12 Pigmentary Glaucoma 7.13 Exfoliative Glaucoma 7.14 Calcium Voltage-Gated Channel Subunit Alpha1 A (CACNA1A) 7.15 Limitations of GWAS 7.16 Genetics in Glaucoma—A Step in Future 7.16.1 Whole Exon/Genome Sequencing 7.16.2 Comparative RNA Sequencing of Tissues 7.16.3 Gene Therapy References 8: Genetics of Retinoblastoma 8.1 Introduction 8.2 Genes Involved in Retinoblastoma 8.2.1 RB1 Gene 8.2.2 Cell Cycle Control 8.2.3 Heterochromatin and Chromosome Stability 8.2.4 Regulation of Apoptosis 8.2.5 MYCN 8.3 Genetic Alterations and Development of Retinoblastoma 8.3.1 The First Hit 8.3.2 The Second Hit 8.3.3 Mutation 3 and Genomic Instability 8.3.4 Epigenetics in Retinoblastoma 8.4 Genotype–Phenotype Correlation 8.5 Genetic Testing 8.5.1 Indications of Genetic Testing 8.5.2 How to Conduct Genetic Testing? 8.5.3 Conclusion References 9: Molecular Mechanisms in the Pathogenesis of Retinopathy of Prematurity (ROP) 9.1 Introduction 9.2 Role of Genetics in Pathophysiology of ROP 9.3 Role of MicroRNAs in the Pathophysiology of ROP 9.4 Major Proteins Involved in the Pathophysiology of ROP 9.5 Insulin-Like Growth Factor-1 9.6 Placental Growth Factor 9.7 Erythropoietin 9.8 Role of Oxidative Stress in ROP Pathophysiology 9.9 Retinopathy of Prematurity and ROS 9.10 ROS, Inflammation and ROP 9.11 ROS, Autophagy, and ROP 9.12 Conclusion References 10: Genetics in Age-Related Macular Degeneration 10.1 Introduction 10.2 Epidemiology 10.3 Etiology 10.4 Genetics 10.5 Pathogenesis of AMD 10.5.1 Immune and Complement System 10.5.2 Lipid Transport 10.5.3 Extracellular Matrix Remodeling 10.5.4 Angiogenesis 10.5.5 Survival and Homeostasis, Including DNA Repair, Apoptosis, and Stress 10.6 Genetic Testing 10.7 Conclusion References 11: Genetics of Rhegmatogenous Retinal Detachment 11.1 Introduction 11.2 Genetics of Conditions Associated with Rhegmatogenous Retinal Detachment 11.3 Genetics of Syndromic Rhegmatogenous Retinal Detachment 11.4 Genetics of Non-syndromicr hegmatogenous Retinal Detachment References 12: An Overview on the Genetic Etiology, Testing, and Therapeutic Options for Retinitis Pigmentosa 12.1 Introduction 12.2 Etiology of RP 12.2.1 Genes Involved in Phototransduction Cascade 12.2.2 Genes Involved in Visual Cycle (Fig. 12.2) 12.2.3 Genes Involved in Ciliary Transport 12.2.4 Genes Involved in Structural Processes 12.3 Genetic Heterogeneity of RP 12.3.1 Mutation Spectrum of RP 12.4 Current Trends in Molecular Diagnostics of RP 12.5 Genetic Modifiers in RP 12.6 Genetic Testing: A Way Forward Toward Better Diagnosis and Screening 12.7 Preimplantation Genetic Diagnosis and Its Implications 12.8 Evolving Treatment for RP 12.8.1 Ongoing Gene Therapy Trials 12.8.2 Potential Treatment Strategy Underway in End-Stage RP Patients 12.8.3 Cell-Based Therapy 12.8.4 In-Vivo Gene Editing References 13: Genetics in High Myopia 13.1 Introduction 13.2 Genetic Characteristics of Myopia 13.3 Epigenetics 13.4 Management of High Myopia 13.4.1 Prevention of Progression 13.4.2 Genetic Counselling 13.5 Conclusion References 14: Genetics in Strabismus 14.1 Introduction 14.2 Etiology 14.3 Comitant Strabismus 14.4 Ethnic Variations 14.5 Family Studies 14.6 Twin Studies 14.7 Linkage Analysis 14.8 Altered Gene Expression 14.9 Gene Imprinting 14.10 Genome Wide Association Studies 14.11 Gene Analysis 14.12 Incomitant Strabismus 14.13 Isoated DRS 14.14 Syndromic DRS 14.15 HOXA1 Mutations 14.16 CFEOM 14.17 Horizontal Gaze Palsy 14.18 Moebius Syndrome 14.19 Conclusion References 15: Gene Therapy in Diabetic Retinopathy 15.1 Introduction 15.2 Pathogenesis and Genetics Involved in DR 15.3 Metabolic Memory Phenomenon 15.4 Epigenetic Modifications in DR 15.5 Candidate Gene Analysis 15.6 Gene Wide Association Studies (GWAS) 15.7 Limitations in Currents Treatments for DR 15.8 Gene Therapies for DR 15.9 Vectors of Gene Therapy 15.10 Targeting Retinal Vasculopathy 15.11 Vascular and Neuronal Protection 15.12 Future Directions 15.13 Conclusion References 16: Principles of Genetic Counseling in Eye Diseases 16.1 Introduction 16.2 Components of Genetic Counseling 16.2.1 Gathering Information and Pedigree Drawing 16.2.2 Establishing a Genetic Diagnosis 16.2.3 Risk Assessment 16.2.3.1 Autosomal Dominant 16.2.3.2 Autosomal Recessive 16.2.4 X-Linked Inheritance 16.2.4.1 X-Linked Recessive 16.2.4.2 X-Linked Dominant 16.2.4.3 Mitochondrial Inheritance 16.2.4.4 Digenic Inheritance 16.2.4.5 Psychosocial Counseling 16.3 Common Counseling Scenarios That Illustrate the Various Principles of Genetic Counseling 16.3.1 Case Scenario 1: Previous Child with Bilateral Retinoblastoma 16.3.1.1 Genetic Counseling 16.3.2 Case Scenario 2: Previous Child with Cataract and a Positive Family History of Cataract 16.3.2.1 Genetic Counseling 16.3.3 Case Scenario 3: Leber’s Hereditary Optic Neuropathy (LHON) 16.3.3.1 Genetic Counseling 16.3.4 Case Scenario 4: Retinitis Pigmentosa 16.3.4.1 Genetic Counseling 16.3.5 Case Scenario 5: Leber’s Congenital Amaurosis (LCA) 16.3.5.1 Genetic Counseling 16.3.6 Case Scenario 6: Norrie Disease, X-Linked Disorder 16.3.6.1 Genetic Counseling 16.3.7 Case Scenario 7: Stickler Syndrome 16.3.7.1 Genetic Counseling 16.4 Conclusion References