Genetics of Epilepsy

1st Edition - September 2, 2014

Editor: Ortrud Steinlein

Hardback ISBN:

9 7 8 - 0 - 4 4 4 - 6 3 3 2 6 - 2

eBook ISBN:

9 7 8 - 0 - 4 4 4 - 6 3 3 3 3 - 0

The book chapters cover different aspects of epilepsy genetics, starting with the "classical" concept of epilepsies as ion channel disorders. The second part of the book gives… Read more

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The book chapters cover different aspects of epilepsy genetics, starting with the "classical" concept of epilepsies as ion channel disorders. The second part of the book gives credit to the fact that by now non-ion channel genes are recognized as equally important causes of epilepsy. The concluding chapters are designed to offer the reader insight into current methods in epilepsy research. Each chapter is self-contained and deals with a selected topic of interest.

Preface
Chapter 1: Genetic heterogeneity in familial nocturnal frontal lobe epilepsy
- Abstract
- 1 Introduction
- 2 CHRNA4 and CHRNB2: The “Classical” ADNFLE Genes
- 3 The Clinical Spectrum of nAChR-Caused ADNFLE
- 4 CHRNA2: A Rare Cause of Familial NFLE
- 5 Biopharmacological Profiles of nAChR Mutations
- 6 Severe ADNFLE Caused by KCNT1 Mutations
- 7 DEPDC5 as a Cause of Familial Focal Epilepsy
- 8 Conclusions
Chapter 2: Potassium channel genes and benign familial neonatal epilepsy
- Abstract
- 1 Introduction
- 2 Potassium Channels
- 3 Biology of KCNQ2 and KCNQ3 Channels
- 4 Antiepileptic Therapies Targeting K_V7 Channels
- 5 Conclusions
Chapter 3: Mutant GABA_A receptor subunits in genetic (idiopathic) epilepsy
- Abstract
- 1 GABA_A Receptors
- 2 Mutations and Genetic Variations of the GABA_A Receptor
- 3 Mutations of the α Subunit
- 4 Mutations of the β Subunit
- 5 Mutations of the γ Subunit
- 6 Mutations of the δ Subunit
- 7 Therapeutic Implications of GABA_A Receptor Mutations
- 8 Conclusions
- Acknowledgment
Chapter 4: The role of calcium channel mutations in human epilepsy
- Abstract
- 1 Introduction
- 2 Calcium Channel Nomenclature and Biophysical Properties
- 3 Calcium Channels in Epilepsy
- 4 Conclusion
Chapter 5: Mechanisms underlying epilepsies associated with sodium channel mutations
- Abstract
- 1 Introduction
- 2 Voltage-gated Sodium Channels
- 3 Clinical Phenotypes Associated with Voltage-gated Sodium Channel Mutations
- 4 Pathogenetic Mechanisms of Sodium Channel Mutations in Epilepsy
- 5 Conclusions
Chapter 6: The progressive myoclonus epilepsies
- Abstract
- 1 Neuronal Ceroid Lipofuscinoses
- 2 Unverricht–Lundborg Disease
- 3 Lafora Disease
- 4 Type I Sialidosis
- 5 Neuronopathic Gaucher Disease
- 6 Action Myoclonus–Renal Failure Syndrome
- 7 Myoclonus Epilepsy with Ragged Red Fibers
- 8 Dentatorubropallidoluysian Atrophy
- 9 North Sea PME
- 10 Spinal Muscular Atrophy–PME
- Acknowledgments
Chapter 7: Genetics advances in autosomal dominant focal epilepsies: focus on DEPDC5
- Abstract
- 1 Autosomal Dominant Focal Epilepsy Syndromes
- 2 DEPDC5, A Common Cause for Familial Focal Epilepsies
- 3 Conclusions
- Acknowledgments
Chapter 8: PRRT2: A major cause of infantile epilepsy and other paroxysmal disorders of childhood
- Abstract
- 1 Introduction
- 2 PRRT2-Related Syndromes
- 3 Other Forms of Infantile Seizures
- 4 Familial HM
- 5 Intellectual Disability
- 6 PRRT2 Mutations
- 7 PRRT2 Protein and Function
- 8 Conclusions
Chapter 9: LGI1: From zebrafish to human epilepsy
- Abstract
- 1 Introduction
- 2 The LGI1-Related Epilepsy Syndrome
- 3 The LGI1 Gene
- 4 LGI1 Mutant Null Mice Experience Spontaneous Seizures
- 5 Lgi1 Depletion Causes Seizure-Like Behavior in Zebrafish
- 6 Role for LGI in Synaptic Transmission
- 7 Protein Interactions with LGI1 Define Specific Functions
- 8 LGI1 Auto Antibodies Are Responsible for Limbic Encephalitis
- 9 LGI1 Expression Suggests a Role in Early Development
- 10 Role for LGI1 in Normal Mammalian Brain Development
- 11 Are the Other LGI1 Family Members Responsible for Seizure Phenotypes?
- 12 Summary
Chapter 10: Morphogenesis timing of genetically programmed brain malformations in relation to epilepsy
- Abstract
- 1 Introduction
- 2 Concept of Maturational Arrest, Delay, and Precociousness
- 3 Application of Timing to Epileptogenic FCDs
- 4 Timing in Systemic Genetic/metabolic Diseases That Affect Cerebral Development
- 5 Infantile Tauopathies, Microtubules, and Pathogenesis of Dysplasias Involving Cytological Abnormalities of Neurons
- 6 Why Are Cortical Dysplasias Epileptogenic?
- Acknowledgment
Chapter 11: Remind me again what disease we are studying? A population genetics, genetic analysis, and real data perspective on why progress on identifying genetic influences on common epilepsies has been so slow
- Abstract
- 1 Introduction
- 2 A Review of the Methods Used to Find Epilepsy-Related Genes
- 3 A Tale of Three Loci
- 4 What Can Studying CNVs Tell Us about Common Epilepsy?
- 5 Why Rare Mutations Do Not Cause Common Disease
- 6 What the Tale of Three Loci and the Results of CNV Studies Tell Us about Common Epilepsy
- 7 Conclusion
- Acknowledgments
Chapter 12: Monogenic models of absence epilepsy: windows into the complex balance between inhibition and excitation in thalamocortical microcircuits
- Abstract
- 1 Introduction
- 2 Monogenic Mutations of Diverse Genes Converge on the Absence Epilepsy Phenotype
- 3 The Thalamocortical Loop: A Multisynaptic Framework for Interpreting Absence Epilepsy Mutations
- 4 Thalamocortical T-type Calcium Channels: Necessary and Sufficient?
- 5 The Role of Tonic Inhibition: A Key to Unlock T-Type Calcium Channels
- 6 P/Q-Type Calcium Channels: Selective Impairment of Inhibitory Release?
- 7 AMPA Receptor-Related Mutations: Silencing Fast Feedforward Inhibition
- 8 GABA_A Receptor Mutations: Fast Synaptic Disinhibition
- 9 Feedforward Disinhibition: A Preeminent Role in Absence Epilepsy
- 10 Specificity of “Fast” Feedforward Disinhibition in Absence Epilepsy
- 11 Secondary Compensatory Changes with Impaired Feedforward Inhibition
- 12 Pharmacologic Models of Absence Epilepsy Arise from Either Direct Enhancement of Tonic Inhibition or Indirectly via Feedforward Disinhibition
- 13 Other Monogenic Models
- 14 Continuing Challenges
- Acknowledgments
Chapter 13: New technologies in molecular genetics: the impact on epilepsy research
- Abstract
- 1 Genetics Versus Genomics
- 2 Basics Concepts and the Genome in Numbers
- 3 Summary
Chapter 14: Epigenetic mechanisms in epilepsy
- Abstract
- 1 “Bookmarking” the Genome
- 2 Chromatin Structure
- 3 DNA Methylation: Strategy for Transcriptional Silencing
- 4 Histone Modifications: Determinants of Accessibility
- 5 ncRNAs: No Longer Junk
- 6 Epigenetics in CNS Development and Higher Order Brain Function
- 7 Epigenetics in Idiopathic Generalized Epilepsy and Epileptic Encephalopathies
- 8 Epigenetics in TLE
- 9 Metabolism and the Epigenome
- 10 Balancing the Epigenome: Therapeutic Strategies
- 11 Summary
Index
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