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.
Author(s): H. V. Nema, Nitin Nema
Publisher: Springer
Year: 2022
Language: English
Pages: 221
City: Singapore
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
