Genetics of epilepsy:
Gespeichert in:
| Format: | Buch |
|---|---|
| Sprache: | English |
| Veröffentlicht: |
Amsterdam [u.a.]
Elsevier
2014
|
| Ausgabe: | 1. ed. |
| Schriftenreihe: | Progress in brain research
213 |
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | Includes bibliographical references and index |
| Beschreibung: | XV, 329 S. Ill., graph. Darst. 25 cm |
| ISBN: | 9780444633262 044463326X |
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| 650 | 4 | |a Epilepsy / etiology | |
| 650 | 4 | |a Epilepsy / Genetic aspects | |
| 650 | 4 | |a Epilepsy / Etiology | |
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Datensatz im Suchindex
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| adam_text | Titel: Genetics of epilepsy
Autor: Steinlein, Ortrud K
Jahr: 2014
Contents
Contributors...............................................................................................................v
Preface....................................................................................................................vii
CHAPTER 1 Genetic Heterogeneity in Familial Nocturnal
Frontal Lobe Epilepsy..............................................................1
Ortrud K. Steinlein
1. Introduction.....................................................................................1
2. CHRNA4 and CHRNB2: The classical ADNFLE Genes...........2
3. The Clinical Spectrum of nAChR-Caused ADNFLE....................4
4. CHRNA2: A Rare Cause of Familial NFLE..................................5
5. Biopharmacological Profiles of nAChR Mutations.......................6
6. Severe ADNFLE Caused by KCNT1 Mutations...........................6
7. DEPDC5 as a Cause of Familial Focal Epilepsy...........................9
8. Conclusions...................................................................................11
References.....................................................................................11
CHAPTER 2 Potassium Channel Genes and Benign
Familial Neonatal Epilepsy..................................................17
Snezana Maljevic, Holger Lerche
1. Introduction...................................................................................17
2. Potassium Channels......................................................................19
2.1. How Potassium Channels Regulate Neuronal
Excitability?..........................................................................20
2.2. Potassium Channels in Epilepsy and Related
Disorders...............................................................................21
3. Biology of KCNQ2 and KCNQ3 Channels.................................22
3.1. Meet the KCNQs..................................................................22
3.2. Structural and Functional Hallmarks of
Kv7.2/3 Channels.................................................................25
3.3. Expression Pattern of Neuronal Kv7 Channels...................28
3.4. Insights from the Mouseland................................................28
3.5. Functional Analysis of Disease-Related Mutations.............29
3.6. KCNQ2 and KCNQ3 Channelopathies.................................30
3.7. KCNQ2I3 Mutations in BFNS..............................................30
3.8. KCNQ2-Related EE..............................................................34
3.9. KCNQ2 Mutations and PNH................................................37
4. Antiepileptic Therapies Targeting Kv7 Channels........................38
4.1. The Novel Anticonvulsant Compound Retigabine
Is a Kv7 Channel Opener.....................................................38
Contents
4.2. Novel Therapies Involving Kv Channels.............................41
5. Conclusions...................................................................................43
5.1. Five Things We Learned from KCNQ Channels
Involved in Epilepsy.............................................................43
References.....................................................................................43
CHAPTER 3 Mutant GABAa Receptor Subunits in Genetic
(Idiopathic) Epilepsy..............................................................55
Shinichi Hirose
1. GABAa Receptors........................................................................56
2. Mutations and Genetic Variations of the GABAa Receptor.......58
3. Mutations of the a Subunit...........................................................60
3.1. Mutations of GABRA1..........................................................60
3.2. Mutations of GABRA6..........................................................62
4. Mutations of the p Subunit...........................................................63
4.1. Mutations of GABRB1..........................................................63
4.2. Mutations and Variations of GABRB3.................................64
5. Mutations of the y Subunit...........................................................66
5.1. Mutations in CAE and FS....................................................66
5.2. Mutations in GEFS+.............................................................70
5.3. Mutations in Dravet Syndrome............................................71
5.4. Mutations in Idiopathic Genetic Generalized Epilepsy.......72
6. Mutations of the 5 Subunit...........................................................73
7. Therapeutic Implications of GABAa Receptor Mutations..........74
8. Conclusions...................................................................................75
Acknowledgment..........................................................................76
References.....................................................................................76
CHAPTER 4 The Role of Calcium Channel Mutations
in Human Epilepsy..................................................................87
Antonio Gambardella, Angelo Labate
1. Introduction...................................................................................87
2. Calcium Channel Nomenclature and Biophysical
Properties.......................................................................................88
3. Calcium Channels in Epilepsy.....................................................91
3.1. T-type Calcium Channel Mutations in Epilepsy.................91
3.2. P/Q-type Calcium Channel Mutations in Epilepsy..............92
3.3. Ancillary Subunits of Voltage-Gated Calcium
Channels in Seizure Disorders.............................................94
4. Conclusion.....................................................................................94
References.....................................................................................95
Contents
CHAPTER 5 Mechanisms Underlying Epilepsies Associated
with Sodium Channel Mutations........................................97
Ortrud K. Steinlein
1. Introduction...................................................................................97
2. Voltage-Gated Sodium Channels.................................................98
3. Clinical Phenotypes Associated with Voltage-Gated
Sodium Channel Mutations........................................................100
4. Pathogenetic Mechanisms of Sodium Channel
Mutations in Epilepsy.................................................................102
5. Conclusions.................................................................................104
References...................................................................................105
CHAPTER 6 The Progressive Myoclonus Epilepsies........................113
Berge A. Minassian
1. Neuronal Ceroid Lipofuscinoses................................................114
2. Unverricht-Lundborg Disease....................................................116
3. Lafora Disease............................................................................117
4. Type I Sialidosis.........................................................................118
5. Neuronopathic Gaucher Disease................................................118
6. Action Myoclonus-Renal Failure Syndrome.............................119
7. Myoclonus Epilepsy with Ragged Red Fibers...........................119
8. Dentatorubropallidoluysian Atrophy..........................................119
9. North Sea PME...........................................................................120
10. Spinal Muscular Atrophy-PME.................................................120
Acknowledgments......................................................................121
References...................................................................................121
CHAPTER 7 Genetics Advances in Autosomal Dominant Focal
Epilepsies: Focus on DEPDC5...........................................123
Stephanie Baulac
1. Autosomal Dominant Focal Epilepsy Syndromes.....................124
1.1. Familial Temporal Lobe Epilepsy......................................124
1.2. Autosomal Dominant Nocturnal Frontal Lobe Epilepsy... 126
1.3. Familial Focal Epilepsy with Variable Foci......................127
2. DEPDC5, A Common Cause for Familial Focal Epilepsies.....129
2.1. Whole-Exome Sequencing Identifies a New Gene...........129
2.2. DEPDC5 Protein.................................................................131
2.3. From Channelopathies to mTORopathies..........................131
3. Conclusions.................................................................................132
Acknowledgments......................................................................133
References...................................................................................133
Contents
CHAPTER 8 PRRT2: A Major Cause of Infantile Epilepsy
and Other Paroxysmal Disorders of Childhood...........141
Carlo Nobile, Pasquale Striano
1. Introduction.................................................................................141
2. PRRT2-Related Syndromes........................................................142
2.1. PKD.....................................................................................142
2.2. BFIS....................................................................................143
2.3. ICCA Syndrome.................................................................144
2.4. PNKD and PED..................................................................144
3. Other Forms of Infantile Seizures..............................................145
3.1. EA.......................................................................................145
4. Familial HM................................................................................145
5. Intellectual Disability..................................................................146
6. PRRT2 Mutations.......................................................................146
7. PRRT2 Protein and Function......................................................152
8. Conclusions.................................................................................153
References...................................................................................154
CHAPTER 9 LGI1: From Zebrafish to Human Epilepsy......................159
John K. Cowell
1. Introduction.................................................................................160
2. The LGIl-Related Epilepsy Syndrome......................................160
3. The LGI1 Gene...........................................................................161
4. LGI1 Mutant Null Mice Experience Spontaneous Seizures......163
5. Lgil Depletion Causes Seizure-Like Behavior in Zebrafish.....164
6. Role for LGI in Synaptic Transmission.....................................165
7. Protein Interactions with LGI1 Define Specific Functions.......166
8. LGI1 Auto Antibodies Are Responsible for Limbic
Encephalitis.................................................................................167
9. LGI1 Expression Suggests a Role in Early Development.........168
10. Role for LGI1 in Normal Mammalian Brain Development......170
11. Are the Other LGI1 Family Members Responsible
for Seizure Phenotypes?.............................................................172
12. Summary.....................................................................................173
References...................................................................................173
CHAPTER 10 Morphogenesis Timing of Genetically
Programmed Brain Malformations in
Relation to Epilepsy.............................................................181
Harvey B. Sarnat, Laura Flores-Sarnat
1. Introduction.................................................................................182
Contents xiii
2. Concept of Maturational Arrest, Delay, and
Precociousness............................................................................182
3. Application of Timing to Epileptogenic FCDs..........................184
3.1. Developmental Basis of Focal Cortical Dysplasia
Type 1.................................................................................184
4. Timing in Systemic Genetic/metabolic Diseases
That Affect Cerebral Development............................................187
5. Infantile Tauopathies, Microtubules, and Pathogenesis of
Dysplasias Involving Cytological Abnormalities
of Neurons...................................................................................188
6. Why Are Cortical Dysplasias Epileptogenic?............................191
Acknowledgment........................................................................192
References...................................................................................192
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............................................199
David A. Greenberg, William L. Stewart
1. Introduction.................................................................................200
2. A Review of the Methods Used to Find
Epilepsy-Related Genes..............................................................201
2.1. Large-Family Approach.....................................................201
2.2. Association Analysis..........................................................202
2.3. Small-Family Linkage Approach.......................................202
2.4. Comments on the Three Methods......................................203
3. A Tale of Three Loci..................................................................205
3.1. BRD2...................................................................................205
3.2. ELP4 and Centrotemporal Spikes/Rolandic
Epilepsy..............................................................................206
3.3. JME in Mexicans and EFHC1...........................................207
3.4. What We Learn from the Tale of Three Loci...................208
4. What Can Studying CNVs Tell Us about Common
Epilepsy?.....................................................................................209
5. Why Rare Mutations Do Not Cause Common Disease.............211
6. What the Tale of Three Loci and the Results of CNV
Studies Tell Us about Common Epilepsy..................................213
7. Conclusion...................................................................................214
Acknowledgments......................................................................215
References...................................................................................215
xiv Contents
CHAPTER 12 Monogenic Models of Absence Epilepsy:
Windows into the Complex Balance Between
Inhibition and Excitation in Thalamocortical
Microcircuits..........................................................................223
Atul Maheshwari, Jeffrey L. Noebels
1. Introduction.................................................................................224
2. Monogenic Mutations of Diverse Genes Converge
on the Absence Epilepsy Phenotype..........................................225
3. The Thalamocortical Loop: A Multisynaptic Framework
for Interpreting Absence Epilepsy Mutations............................229
4. Thalamocortical T-type Calcium Channels: Necessary
and Sufficient?............................................................................229
5. The Role of Tonic Inhibition: A Key to Unlock
T-Type Calcium Channels..........................................................231
6. P/Q-type Calcium Channels: Selective Impairment
of Inhibitory Release?.................................................................233
7. AMPA Receptor-Related Mutations: Silencing
Fast Feedforward Inhibition.......................................................236
8. GABAa Receptor Mutations: Fast Synaptic
Disinhibition................................................................................237
9. Feedforward Disinhibition: A Preeminent Role
in Absence Epilepsy...................................................................238
10. Specificity of Fast Feedforward Disinhibition
in Absence Epilepsy...................................................................239
11. Secondary Compensatory Changes with Impaired
Feedforward Inhibition...............................................................239
12. Pharmacologic Models of Absence Epilepsy Arise
from Either Direct Enhancement of Tonic Inhibition
or Indirectly via Feedforward Disinhibition..............................240
13. Other Monogenic Models...........................................................241
14. Continuing Challenges................................................................242
Acknowledgments......................................................................243
References...................................................................................243
CHAPTER 13 New Technologies in Molecular Genetics:
The Impact on Epilepsy Research...................................253
Ingo Helbig
1. Genetics Versus Genomics.........................................................253
2. Basics Concepts and the Genome in Numbers..........................255
2.1. Exome—A Technical, not a Philosophical Term..............255
2.2. The Genome in Numbers...................................................256
Contents
2.3. The Third Beast—Rare Genetic Variants..........................256
2.4. Microdeletions—The Search for Epilepsy-Associated
Variants Goes Genome Wide.............................................257
2.5. Recurrent and Nonrecurrent Microdeletions......................258
2.6. Microdeletions from Genomic Disorders to
Genome-First......................................................................259
2.7. Variant Classification and the Global Burden of
Microdeletions in Epilepsy.................................................261
2.8. Genome-Wide Association Studies—The Late Success ...262
2.9. Massive Parallel Sequencing Studies.................................263
3. Summary.....................................................................................268
References...................................................................................269
CHAPTER 14 Epigenetic Mechanisms in Epilepsy..............................279
Katja Kobow, Ingmar Bliimcke
1. Bookmarking the Genome......................................................279
2. Chromatin Structure....................................................................280
3. DNA Methylation: Strategy for Transcriptional Silencing........280
4. Histone Modifications: Determinants of Accessibility..............283
5. ncRNAs: No Longer Junk..........................................................285
5.1. Small ncRNAs....................................................................286
5.2. Long ncRNAs.....................................................................287
6. Epigenetics in CNS Development and Higher Order
Brain Function............................................................................288
7. Epigenetics in Idiopathic Generalized Epilepsy and
Epileptic Encephalopathies.........................................................289
8. Epigenetics in TLE.....................................................................293
9. Metabolism and the Epigenome.................................................297
10. Balancing the Epigenome: Therapeutic Strategies....................301
11. Summary.....................................................................................303
References...................................................................................303
Index.......................................................................................................................317
Other volumes in PROGRESS IN BRAIN RESEARCH..............................................327
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| id | DE-604.BV042425145 |
| illustrated | Illustrated |
| indexdate | 2024-07-10T01:21:16Z |
| institution | BVB |
| isbn | 9780444633262 044463326X |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-027860542 |
| oclc_num | 905458364 |
| open_access_boolean | |
| owner | DE-19 DE-BY-UBM |
| owner_facet | DE-19 DE-BY-UBM |
| physical | XV, 329 S. Ill., graph. Darst. 25 cm |
| publishDate | 2014 |
| publishDateSearch | 2014 |
| publishDateSort | 2014 |
| publisher | Elsevier |
| record_format | marc |
| series | Progress in brain research |
| series2 | Progress in brain research |
| spelling | Genetics of epilepsy ed. by Ortrud K. Steinlein 1. ed. Amsterdam [u.a.] Elsevier 2014 XV, 329 S. Ill., graph. Darst. 25 cm txt rdacontent n rdamedia nc rdacarrier Progress in brain research 213 Includes bibliographical references and index Epilepsy / genetics Epilepsy / etiology Epilepsy / Genetic aspects Epilepsy / Etiology Epilepsy / Etiology fast Epilepsy / Genetic aspects fast Genetik (DE-588)4071711-2 gnd rswk-swf Ätiologie (DE-588)4000646-3 gnd rswk-swf Epilepsie (DE-588)4015035-5 gnd rswk-swf Epilepsie (DE-588)4015035-5 s Genetik (DE-588)4071711-2 s DE-604 Ätiologie (DE-588)4000646-3 s Steinlein, Ortrud K. Sonstige oth Progress in brain research 213 (DE-604)BV008000363 213 HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027860542&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Genetics of epilepsy Progress in brain research Epilepsy / genetics Epilepsy / etiology Epilepsy / Genetic aspects Epilepsy / Etiology Epilepsy / Etiology fast Epilepsy / Genetic aspects fast Genetik (DE-588)4071711-2 gnd Ätiologie (DE-588)4000646-3 gnd Epilepsie (DE-588)4015035-5 gnd |
| subject_GND | (DE-588)4071711-2 (DE-588)4000646-3 (DE-588)4015035-5 |
| title | Genetics of epilepsy |
| title_auth | Genetics of epilepsy |
| title_exact_search | Genetics of epilepsy |
| title_full | Genetics of epilepsy ed. by Ortrud K. Steinlein |
| title_fullStr | Genetics of epilepsy ed. by Ortrud K. Steinlein |
| title_full_unstemmed | Genetics of epilepsy ed. by Ortrud K. Steinlein |
| title_short | Genetics of epilepsy |
| title_sort | genetics of epilepsy |
| topic | Epilepsy / genetics Epilepsy / etiology Epilepsy / Genetic aspects Epilepsy / Etiology Epilepsy / Etiology fast Epilepsy / Genetic aspects fast Genetik (DE-588)4071711-2 gnd Ätiologie (DE-588)4000646-3 gnd Epilepsie (DE-588)4015035-5 gnd |
| topic_facet | Epilepsy / genetics Epilepsy / etiology Epilepsy / Genetic aspects Epilepsy / Etiology Genetik Ätiologie Epilepsie |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027860542&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| volume_link | (DE-604)BV008000363 |
| work_keys_str_mv | AT steinleinortrudk geneticsofepilepsy |