Diseases of DNA Repair (eBook)

SHAMIM AHMAD (Herausgeber)

eBook Download: PDF

2011 | 2010
XXVII, 256 Seiten
Springer New York (Verlag)
978-1-4419-6448-9 (ISBN)

Infos

Since this book is geared to be used by varied groups of readers such as advanced students and instructors in the fields of biology and medicine, scientists and more importantly clinicians, it is considered important to provide brief accounts of the basics of DNA damage, repair, mutagenesis and cancer. The purpose of this book is to present an updated detailed account of some important additional diseases of DNA repair. It has not been possible to cover all the DNA repair deficient diseases in this volume, hence diseases such as Bloom's syndrome, Werner's syndrome, Nijmegen breakage syndrome, ataxia telangiectasia-like disorder, RA D 50 deficiency, RIDDLE syndrome and others will be presented in a forthcoming volume.

Shamim Ahmad after obtaining his Master's degree in Botany from Patna University, Bihar, India and his PhD in Molecular Genetics from Leicester University, England, joined Nottingham Polytechnic as Grade 1 lecturer and subsequently promoted to SL post. Nottingham Polytechnic subsequently became Nottingham Trent University where, after serving for about 35 years, he took early retirement to spend the remaining time writing books and conducting full-time research. For more than three decades he worked on different areas of biology including thymineless death in bacteria, genetic control of nucleotide catabolism, development of anti-AIDS drugs, control of microbial infection of burns, phages of thermophilic bacteria and microbial flora of Chernobyl after nuclear accident. But his primary interest, which started 25 years ago, is DNA damage and repair, particularly near UV photolysis of biological compounds, production of reactive oxygen species and their implications on human health including skin cancer and xeroderma pigmentosum. He is also investigating photolysis of non-biological compounds such as 8-methoxypsoralen+UVA, mitomycin C, and nitrogen mustard and their importance in psoriasis treatment and in Fanconi anemia. In 2003 he received a prestigious 'Asian Jewel Award' in Britain for 'Excellence in Education'. He is also the Editor of Molecular Mechanisms of Fanconi Anaemia, Molecular Mechanisms of Xeroderma Pigmentosum, Molecular Mechanisms of Ataxia Telangiectasia and Molecular Mechanisms of Cockayne Syndrome published by Landes Bioscience.

Inhalt

Title Page 3
Copyright Page 4
DEDICATION TO A SPECIAL PERSON—AMY 5
PREFACE 7
ABOUT THE EDITOR... 13
PARTICIPANTS 14
Table of Contents 20
ACKNOWLEDGEMENTS 26
Chapter 1 Triple-A Syndrome 27
Introduction 27
Epidemiology 27
Etiology 28
Pathology 30
Clinical Manifestations 30
Diagnosis 31
Differential Diagnosis 31
Treatment 32
Conclusion 32
References 33
Chapter 2 Amyotrophic Lateral Sclerosis 35
Introduction 35
Clinical Features 35
Genetic Basis and the Molecular Mechanism of the Disease 36
Cu,ZnSOD 37
TDP-43 38
FUS/TLS 40
Conclusion 42
References 43
Chapter 3 Early-Onset Ataxia with Ocular Motor Apraxia and Hypoalbuminemia/Ataxia with Oculomotor Apraxia 1 47
Introduction 47
Synonyms and Historical Annotations 48
Epidemiology 48
Incidence and Prevalence 48
Sex and Age Distribution 49
Risk Factors 49
Genetics of EAOH/AOA1 49
Genotype and Phenotype Correlation 50
Clinical Features 50
Signs and Symptoms 50
OMA in EAOH/AOA1 50
Imaging and Laboratory Findings 51
Neuropathological Features 52
Differential Diagnosis 53
Pathogenesis 54
Function of Aprataxin 54
Defects in SSBR and Neurodegeneration 54
Experimental Models 55
Conclusion 56
References 57
Chapter 4 Clinical Features and Pathogenesis of Alzheimer’s Disease: Involvement of Mitochondria and Mitochondrial DNA 60
Alzheimer’s Disease 60
Mitochondrial Structure and Function 62
Oxidative Stress and Mitochondrial Dysfunction in AD 63
The Role of Mitochondrial DNA 66
Conclusion 67
References 68
Chapter 5 Huntington’s Disease 71
History 71
Clinical Aspects 71
Movement Disorders 72
Cognitive Impairment 72
Psychiatric Disorders 72
Other Clinical Manifestations 72
Genetic Aspects 73
Neuropathology 74
Molecular Mechanisms 74
Aggregates 75
Transcriptional Dysregulation 75
Excitotoxicity 76
Changes in Axonal Transport and Synaptic Function 78
Mitochondrial Dysfunction and Altered Energy Metabolism 78
Conclusion 79
References 79
Chapter 6 Clinical Features and Molecular Mechanisms of Spinal and Bulbar Muscular Atrophy (SBMA) 90
Clinical Features 90
Genetic Basis 91
Histopathology 92
Molecular Mechanisms 92
Aggregation of Mutant Androgen Receptor 92
Testosterone-Dependent Neurodegeneration in SBMA 93
Transcriptional Dysregulation 93
Disruption of Axonal Transport 94
Mitochondrial Dysfunction 94
Noncell Autonomous Toxicity of Lower Motor Neurons 94
Therapeutic Strategies 94
Testosterone Deprivation Therapy 94
Manipulation of Heat Shock Proteins and Ubiquitin Proteasome System 95
Restoration of Transcriptional Activity 96
Conclusion 96
References 98
Chapter 7 Spinocerebellar Ataxia with Axonal Neuropathy 101
Introduction 101
Symptoms of SCAN1 104
Genetic Basis of SCAN1 104
Tdp1 Function 104
Molecular Basis of SCAN1 105
Current and Future Research 105
Conclusion 107
References 107
Chapter 8 Tuberous Sclerosis Complex and DNA Repair 110
Introduction: Clinical Manifestations of TSC Disease 110
Renal Lesions in TSC-Deficient Mammals 111
Mouse 111
Rat 111
Human 111
TSC1 and TSC2 Genes 113
TSC Genes and Cell Signals 113
TSC Genes and Akt 113
TSC genes and ERK/AMPK 114
TSC Genes and mTOR 115
TSC and DNA Damage/Repair Pathway 116
DNA Damage/Repair Pathway and Cancer 116
TSC2 Regulates DNA Damage/Repair Pathway 116
Conclusion 117
References 117
Chapter 9 Hereditary Photodermatoses 121
Introduction 121
Metabolic Photodermatoses 122
Porphyrias 122
Hartnup Disease 122
Smith-Lemli-Opitz Syndrome (SLO) 122
Hereditary Photodermatoses of Unknown Etiology or Pathogenesis 124
Kindler Syndrome 124
Actinic Prurigo 124
Polymorphous Light Eruption (PMLE) 124
Solar Urticaria 124
Chronic Actinic Dermatitis 125
Hydroa Vacciniforme 125
Defects in Cancer Suppressor Genes 125
Basal Cell Nevus Syndrome (Gorlin Syndrome) 125
Familial Melanoma 125
Human Syndromes Defective in DNA Repair 125
Photodermatoses and Defects in DNA Helicases 126
Bloom’s Syndrome 126
Rothmund-Thomson Syndrome (RTS) or Poikiloderma Congenitale 126
Photodermatoses and Defects in DNA Damage Response Pathways 126
Photodermatoses and Defects in NER 127
UV-Sensitive Syndrome (UVSS) 127
Response of UVSS Cells to UV Irradiation 128
Response of UVSS and CS Cells to Oxidative DNA Damage 128
UVSS Complementation Groups 128
Conclusion 129
References 130
Chapter 10 Trichothiodystrophy: Photosensitive, TTD-P, TTD, Tay Syndrome 132
Clinical Manifestations 132
Xeroderma Pigmentosum/Trichothiodystrophy Overlap Syndrome 133
Cockayne Syndrome/Trichothiodystrophy Overlap Syndrome 133
Etiopathogenesis 133
Laboratory Diagnosis 134
Animal Model 135
Conclusion 135
References 135
Chapter 11 Cornelia de Lange Syndrome 137
Clinical Characteristics 137
Introduction 137
CdLS in Adolescents and Adults 139
Prenatal Presentation and Recurrence Risks 139
Molecular Genetics of CdLS 139
Roles of NIPBL, SMC1A and SMC3 in CdLS 139
Molecular Genetics of NIPBL, SMCA1 and SMC3 140
Cohesin Biology 141
Cohesin and Its Accessory Proteins in Transcriptional Regulation 143
Cohesin and Chromatin Remodeling 144
Other Cohesinopathies 145
Conclusion 145
References 145
Chapter 12 Rectal Cancer and Importance of Chemoradiation in the Treatment 150
Introduction 150
Rectal Cancer: Metastasis and Survival Rates 151
Mechanisms of Cell Death By Ionizing Radiation 152
Mechanisms of Resistance to Radiation in Rectal Cancer 152
Cell Cycle 152
Proliferation Markers and Mitotic Index (Ki-67) 153
p53, p21 and p27 and Apoptotic Index (AI) 153
Apoptosis 154
NF B 156
Inhibitors of Apoptosis (IAPs: Survivin) 156
Conclusion 157
References 157
Chapter 13 Familial Cutaneous Melanoma 160
Introduction 160
Risk Factors for Melanoma 160
Familial Melanoma—The Clinical Picture 160
Molecular Genetics of Familial Cutaneous Melanoma 162
High Risk Melanoma Genes 162
CDKN2A 162
CDK4 165
Candidate Loci for Novel Genes Predisposing to Familial CMM 165
Risk of Melanoma and Other Cancers in Melanoma Families with Germline CDKN2A Mutations 165
Genetic Testing in Familial Melanoma 166
Management of Familial Melanoma 166
Primary Prevention 167
Secondary Prevention of CMM 167
Pancreatic Carcinoma Surveillance 168
Conclusion 168
References 168
Chapter 14 Primary Immunodeficiency Syndromes 172
Introduction 172
Role of DNA Repair Proteins in Adaptive Immunity 172
Generation of Lymphocyte Antigen Receptors 172
Immunoglobulin Class Switch Recombination 173
Somatic Hypermutation 176
Genetic Defects Associated with Primary Immunodeficiency Syndromes 176
Genetic Defects Critical for Lymphocyte Development 176
Recombination Activating Gene 1 and 2 176
Artemis Deficiency 176
DNA-PK Deficiency 179
DNA Ligase 4 Deficiency 179
Cernunnos-XLF Deficiency 180
Primary Immunodeficiency Associated with Disorders in DNA-dsb Damage Sensing Proteins 181
Ataxia Telangiectasia 181
Nijmegen Breakage Syndrome 181
Ataxia telangiectasia-Like Disorder 182
RAD50 Deficiency 183
Radiosensitivity, Immunodeficiency, Dysmorphic Features and Learning Difficulties (RIDDLE) Syndrome 183
Other Uncharacterised Disorders 183
Human Primary Immunodeficiency Due to Genetic Defects in Class Switch Recombination and Somatic Hypermutation 183
Autosomal Recessive Hyper-IgM Syndromes 183
AID Deficiency 183
UNG Deficiency 184
PMS2 Deficiency 184
MSH5 Deficiency 184
Undefined Defects of Class Switch Recombination and Somatic Hypermutation 184
Human Primary Immunodeficiency Due to Genetic Defects in Other DNA Repair Genes 185
DNA Ligase 1 185
Bloom Syndrome 185
Treatment 185
Conclusion 186
References 187
Chapter 15 Inherited Defects of Immunoglobulin Class Switch Recombination 192
Introduction 192
CSR Deficiency Caused by Activation-Induced Cytidine Deaminase (AID)-Defect 193
CSR Deficiency Caused by Uracil-N Glycosylase (UNG)-Defect 194
CSR Deficiency Caused by Post-Meiotic Segregation 2 (PMS2) Defect 195
CSR Deficiency Caused by An Unknown DNA Repair Factor Defect 196
CSR-Deficiency in Molecularly Defined Syndromes Affecting the DNA Repair Machinery 196
Conclusion 197
References 197
Chapter 16 Ligase IV Syndrome 201
Ligase IV Syndrome: Clinical Features 201
DNA Ligase IV Is a Component of Nonhomologous End-Joining Pathway of DNA Repair 201
DNA Ligase IV: Structure and Function 203
Animal Models with Genetic Defects in Lig4 205
Ligase IV Mutations Causing LIG4 Syndrome in Humans 205
Mutation R278H 205
Mutation G469E 206
Mutation M249V 206
Frameshift Mutation (K424FS) 206
Mutation Q280R 206
Truncating Mutations (R580X and R814X) 206
N-Terminal Polymorphisms (A3V and T9I) 208
LIG4 Mutations Associated with Severe Combined Immunodeficiency 209
Conclusion 209
References 210
Chapter 17 Muir-Torre Syndrome 212
Introduction 212
Histopathology 213
Sebaceous Adenoma 213
Sebaceous Epithelioma 214
Sebaceoma 215
Basal Cell Carcinoma with Sebaceous Differentiation 215
Sebaceous Carcinoma 215
Keratoacanthoma 215
Clinical Features 215
Genetics of Muir Syndrome 218
Conclusion 218
Acknowledgement 218
References 219
Chapter 18 Wilms’ Tumor 222
Introduction 222
Epidemiology 222
Genetic Basis and the Molecular Mechanism of the Disease 223
WT1 223
Isoforms 223
Transcription Regulator 223
Developmental Role 223
Tumorogenesis 223
WT2 223
WT3 224
WTX 224
p53 and Others Apoptosis Associated Markers 224
-Catenin 224
Growth Factors 224
Cell Adhesion Molecules 224
Other Markers 224
DNA Repair 225
Familial Wilms’ Tumor 225
Wilms’ Tumor Associated Syndromes 225
Beckwith-Wiedemann Syndrome 225
WAGR Syndrome 225
Denys-Drash Syndrome 225
Perlman Syndrome 226
Histopathology 226
Macroscopic Features 226
Microscopic Features 226
Nephrogenic Rests and Nephroblastomatosis 226
Clinical Features 227
Imaging Studies 228
Ultrasonography 228
Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) 228
Staging 228
Treatment 228
Surgery 228
National Wilms’ Study Group 230
International Society of Paediatric Oncology 230
Analysis of NWTS and SIOP Protocols 231
Bilateral Wilms’ Tumor 231
Adult Wilms’ Tumor 231
Conclusion 231
References 232
Chapter 19 Cerebro-Oculo-Facio-SkeletalSyndrome 236
Introduction 236
Clinical Features 236
Prognosis 237
Differential Diagnosis 237
Neu-Laxova Syndrome 237
Micro Syndrome (Warburg Micro Syndrome) 237
Cockayne Syndrome 237
Cataract, Microcephaly, Failure to Thrive, Kyphoscoliosis (CAMFAK)Syndrome 238
Martsolf Syndrome 238
Genetic Basis and the Molecular Mechanism 238
COFS1: ERCC6 Gene (CSB) at 10q11 238
COFS2: ERCC2 Gene (XPD) at 19q13.2-q13.3 238
COFS3: ERCC5 Gene (XPG) at 13q33 239
COFS4: ERCC1 Gene at 19q13.2-q13.3 239
Conclusion 239
References 240
Chapter 20 Dyskeratosis Congenita 241
Introduction 241
Clinical Features 242
Genetics of DC 242
Genetic Defects 242
Immunological Abnormalities 243
Treatment 243
Prognosis and Outcome 244
Conclusion 244
References 244
Chapter 21 Retinoblastoma 246
Clinical Aspects 246
Epidemiology of Retinoblastoma 246
Diagnosis of Rb 246
Presentation and Family History 247
Therapy and Prognosis 247
Second Cancers in Patients with Hereditary Rb 247
Incidence of Second Cancers 247
Spectrum of Second Cancers 247
Development of Further Tumours after a Second Tumour 248
Ionising Radiation as a Risk Factor 248
Chemotherapy as a Risk Factor 248
Genetic Risk Factors 248
Molecular Genetics 248
Hereditary and Nonhereditary Rb is Caused by Two Mutations 248
Identification of the RB1 Gene 248
The RB1 Gene Encodes a Pocket Protein 249
Tumor Genetics of Rb 249
Phenotypic Consequences of RB1 Gene Mutations 249
Genotype-Phenotype Associations 250
Other Factors That Modify Phenotypic Expression 251
Endophenotypes Observed in Rb Patients 251
Conclusion 252
References 252
Chapter 22 Von Hippel Lindau Syndrome 254
Genetic Basis and Molecular Mechanism of VHLS 254
Identification of the VHL Gene 254
VHL Tumor Suppressor Gene 255
VHL-HIF Biology 255
Non-HIF Related VHLS Pathways 258
E-Cadherin and -Catenin 258
Ciliogenesis 258
Extracellular Matrix Regulation 258
p53 Tumor Suppressor Stabilization and Transactivation 259
Clinical Features 259
Hemangioblastomas of the CNS 260
Retinal Hemangioblastoma 262
Endolymphatic Sac Tumors 262
Renal Cell Carcinomas and Renal Cysts 263
Pheochromocytomas 265
Pancreatic Neuroendocrine Tumors and Cysts 266
Epididymal Cystadenomas 267
Conclusion 268
References 268
Index 276

Produkt-Details

• Erscheint lt. Verlag: 11.1.2011
• Reihe/Serie: Advances in Experimental Medicine and Biology
• Reihe/Serie: Advances in Experimental Medicine and Biology
• Zusatzinfo: XXVII, 256 p.
• Verlagsort: New York
• Sprache: englisch
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete
• Themenwelt: Studium ► 1. Studienabschnitt (Vorklinik) ► Biochemie / Molekularbiologie
• Themenwelt: Studium ► 2. Studienabschnitt (Klinik) ► Humangenetik
• Schlagworte: Ahmad • Disease • DNA • Gen • Genetics • Repair • Retinoblastom • Xeroderma pigmentosum
• ISBN-10: 1-4419-6448-7 / 1441964487
• ISBN-13: 978-1-4419-6448-9 / 9781441964489