Neurogenetics: Scientific and Clinical Advances

by Lynch; David R.

• ISBN13: 9780824729424
• ISBN10: 0824729420
• Edition: 1st
• Format: Hardcover
• Copyright: 2005-11-01
• Publisher: CRC Press

Summary

Children's Hospital, Philadelphia, PA. Text presents current perspectives on neurogenetic disease both from clinical and scientific perspectives. Topics include genetic testing, ethical dilemmas, gene therapy, genetic counseling, and more. For researchers and clinicians.

Table of Contents

Foreword	iii
Preface	v
Contributors	xvii
Neurogenetics in the Clinic	1	(10)
Thomas D. Bird
Factors Suggesting a Neurogenetic Disorder	1	(1)
Neurogenetic Diseases ``Hiding'' in Nonspecific Categories	2	(1)
Importance of Family History	3	(2)
Assessment of Sporadic Cases	5	(1)
Genetic Counseling	6	(2)
Genetic Testing	8	(1)
Neurogenetics Information Resources	8	(1)
An Integrated Clinical Neurogenetics Strategy	9	(1)
References	10	(1)
Genetic Testing for Neurological Disorders	11	(16)
Martha A. Nance
Introduction	11	(1)
Principles of Genetic Inheritance	11	(3)
Genotype Changes and Their Significance in Phenotypic Appearance	14	(1)
Gene Mutations and Assays to Detect Them	15	(2)
Clinical Use of Gene Tests	17	(6)
Resources for the Clinician	23	(1)
References	23	(4)
Genetic Counseling	27	(16)
Robin L. Bennett
Introduction	27	(1)
Are Genetic Disorders Unique?	27	(3)
Who Are Genetic Counselors?	30	(1)
The Process of Genetic Counseling	31	(1)
Genetic Family History---The Pedigree	31	(4)
Pedigree Analysis and Risk Perception	35	(5)
Summary	40	(1)
References	40	(3)
Gene Therapy for Inherited Diseases of the Central Nervous System	43	(44)
Tyler Mark Pierson
John H. Wolfe
Introduction	43	(1)
General Properties of CNS Gene Therapy	44	(1)
Candidate Diseases for Gene Therapy in the CNS	45	(5)
Animal Models of Genetic CNS Disorders	50	(4)
Lysosomal Storage Disease: Animal Models as a Paradigm for CNS Gene Therapy	54	(2)
Gene Delivery Vehicles	56	(11)
Summary	67	(1)
References	68	(19)
Ethical Dilemmas in Neurogenetics	87	(20)
Wendy R. Uhlmann
Testing Minors	89	(1)
Testing a Child for Adoption	89	(2)
Testing an Adult Child When the At-Risk Parent Refuses Testing	91	(1)
Is There a ``Duty to Warn'' and Share Test Results with Other At-Risk Family Members?	92	(1)
Testing Identical Twins	93	(1)
Non-Disclosure of Test Results	94	(1)
Testing Siblings Simultaneously	95	(1)
Testing Individuals Who Work in Professions Where Neurological Deficits Can Jeopardize the Safety of Others	96	(1)
Testing Symptomatic Individuals Who Think They Are Asymptomatic	96	(1)
Testing ``Asymptomatic'' Individuals Who have Recently Attempted Suicide	97	(1)
Testing a Blood Sample from Someone Who Has Just Committed Suicide	98	(1)
Testing a Pregnancy	98	(2)
Giving Informed Consent for Individuals with Cognitive/Psychiatric Impairment	100	(1)
Insurance Issues	101	(1)
Anonymous Testing	101	(1)
Legal Cases	102	(1)
Resources	102	(1)
Summary	102	(1)
Recommended Reading	103	(1)
References	103	(4)
Autosomal Dominant Charcot-Marie-Tooth Disease and Related Disorders	107	(22)
Craig L. Bennett
Scope of This Chapter	107	(1)
CMT: Background and General Clinical Features	107	(1)
Electrophysiological Classification of CMT	108	(1)
Major Forms of Demyelinating CMT1	109	(8)
Major Forms of Demyelinating CMT2	117	(5)
Prognosis in CMT	122	(1)
Summary	122	(1)
Electronic Databases	122	(1)
References	122	(7)
Duchenne and Becker Muscular Dystrophies	129	(28)
Leta S. Steffen
Louis M. Kunkel
Introduction	129	(2)
Clinical Symptoms	131	(1)
Clinical Diagnosis	132	(2)
Clinical Treatment	134	(2)
History of the Dystrophin Discovery	136	(1)
Dystrophin---Molecular Characterization	137	(1)
Animal Models of DMD	138	(1)
Current Research for DMD/BMD Therapies	139	(6)
Conclusion	145	(1)
References	145	(12)
The Congenital and Limb-Girdle Muscular Dystrophies	157	(22)
Janbernd Kirschner
Carsten G. Bonnemann
Introduction	157	(1)
Congenital Muscular Dystrophies	158	(12)
Limb-Girdle Muscular Dystrophies	170	(3)
References	173	(6)
Non-dystrophic Myotonias and Periodic Paralyses	179	(18)
Arie Struyk
Stephen Cannon
Introduction	179	(3)
Chloride Channel Myotonias (Myotonia Congenita)	182	(2)
Sodium Channel Myotonia and Periodic Paralysis	184	(4)
Hypokalemic Periodic Paralysis	188	(3)
Andersen's Syndrome	191	(2)
Conclusions	193	(1)
References	193	(4)
The Myotonic Dystrophies---Effects of an RNA Mutation	197	(16)
John W. Day
Laura P. W. Ranum
Introduction	197	(1)
Clinical Features of the Myotonic Dystrophies	198	(3)
Genetics of the Myotonic Dystrophies	201	(3)
Molecular Pathogenesis of the Myotonic Dystrophies	204	(3)
Reports of a Third Form of Myotonic Dystrophy	207	(1)
Summary	207	(1)
References	208	(5)
Spinal Muscular Atrophy	213	(18)
Stephen J. Kolb
J. Paul Taylor
Introduction	213	(1)
Clinical Features of Autosomal Recessive SMA	214	(1)
Molecular Genetics of Autosomal Recessive SMA	215	(1)
SMA Unrelated to Mutations in SMN1	216	(1)
Basic Research on Autosomal Recessive SMA: The SMN Complex	217	(3)
Model Systems	220	(1)
Therapeutics	220	(3)
References	223	(8)
Hereditary Spastic Paraplegia	231	(30)
Kleopas A. Kleopa
Introduction	231	(1)
Clinical and Pathological Features of HSP	231	(4)
Genetics and Neurobiology of HSP	235	(12)
Diagnostic Approach and Treatment in HSP	247	(1)
Conclusion	248	(1)
References	249	(12)
Mitochondrial Disorders	261	(28)
Clotilde Lagier-Tourenne
Michio Hirano
Introduction	261	(1)
Principles of Mitochondrial Genetics	262	(2)
Primary Mitochondrial DNA Mutations	264	(1)
Nuclear DNA Mutations	265	(4)
General Features of Mitochondrial Diseases	269	(6)
Specific Mitochondrial Diseases	275	(3)
MELAS	278	(4)
References	282	(7)
Friedreich Ataxia	289	(22)
Martin B. Delatycki
Michael C. Fahey
Louise Corben
Andrew Churchyard
Introduction	289	(1)
Clinical Features	289	(3)
Pathology	292	(1)
Molecular Genetics	292	(2)
Pathogenesis	294	(2)
Management of Patients with FRDA	296	(4)
Potential Pharmacological Therapies for FRDA	300	(2)
Conclusion	302	(1)
References	302	(9)
Autosomal Dominant Ataxias	311	(46)
Susan L. Perlman
Introduction	311	(2)
The Typical Dominant Ataxias	313	(1)
SCA1	314	(12)
SCA2	326	(2)
SCA3	328	(1)
SCA4	329	(1)
SCA5	330	(1)
SCA6	330	(2)
SCA7	332	(1)
SCA8	333	(2)
SCA9	335	(1)
SCA10	335	(1)
SCA11	336	(1)
SCA12	336	(1)
SCA13	337	(1)
SCA14	337	(1)
SCA15	338	(1)
SCA16	339	(1)
SCA17	339	(2)
SCA18	341	(1)
SCA19	341	(1)
SCA20	342	(1)
SCA21	343	(1)
SCA22	343	(1)
SCA23	344	(1)
SCA24	344	(1)
SCA25	344	(1)
SCA26	345	(1)
SCA Due to FGF14	345	(1)
Conclusion	346	(1)
References	346	(11)
Huntington's Disease: Mechanisms of Pathogenesis and Development of New Therapies	357	(26)
Blair R. Leavitt
Lynn A. Raymond
Clinical, Pathologic, and Genetic Features of Huntington's Disease	357	(4)
Animal Models of HD	361	(3)
Pathogenesis of HD	364	(5)
Preclinical Trials in Mouse Models of HD	369	(1)
Clinical Trials in HD	370	(3)
Conclusions	373	(1)
References	373	(10)
Wilson's Disease	383	(20)
George J. Brewer
Introduction and Historical Overview	383	(1)
Pathophysiology	384	(1)
Genetics and Epidemiology	384	(2)
Clinical Presentations	386	(3)
Recognition, Screening, and Diagnosis	389	(3)
Treatment with Anticopper Drugs	392	(4)
Prognosis	396	(1)
References	397	(6)
Neurogenetics of Dystonia and Paroxysmal Dyskinesias	403	(24)
Jennifer Friedman
David G. Standaert
Dystonia	403	(4)
Genetics of Primary Dystonias	407	(3)
Genetics of Dystonia Plus Syndromes	410	(5)
Genetics of Paroxysmal Dystonias and Dyskinesias	415	(2)
References	417	(10)
Inherited Epilepsies	427	(42)
Yr Sigurdardottir
Annapurna Poduri
Introduction	427	(1)
Channelopathies	428	(12)
Myoclonic Epilepsies	440	(8)
Generalized Epilepsy Syndromes	448	(2)
Localization-Related Epilepsy Syndromes	450	(2)
Conclusion	452	(1)
References	452	(17)
Leukodystrophies	469	(86)
James Y. Garbern
Introduction	469	(1)
Disorders of Myelin Lipid Metabolism	470	(48)
Closing Thoughts	518	(1)
Resources	518	(1)
References	519	(36)
Lysosomal Storage Disorders	555	(28)
David A. Wenger
Stephanie Coppola
Introduction	555	(1)
General Concepts	556	(2)
Clinical Features that Suggest a LSD	558	(6)
Diagnosis of LSDs	564	(8)
Treatment of LSDs	572	(5)
References	577	(6)
The Tuberous Sclerosis Complex: Clinical Manifestations and Molecular Genetics	583	(16)
John R. Pollard
Peter B. Crino
Clinical Features of TSC	583	(2)
Neurological Manifestations	585	(1)
Neuropathology	586	(1)
Genetics	587	(2)
Signaling Pathway and Cell Biology	589	(3)
Conclusion	592	(1)
References	593	(6)
Neurofibromatosis	599	(22)
Amit Malhotra
James Dowling
David H. Gutmann
Introduction	599	(1)
Neurofibromatosis 1	600	(9)
Clinical Features of Neurofibromatosis 2	609	(3)
References	612	(9)
Genetics of Parkinson's Disease	621	(22)
Sathya R. Sriram
Valina L. Dawson
Ted M. Dawson
Introduction	621	(1)
Genes Linked to Familial PD	622	(11)
Clinical Testing for Genetic Forms of PD	633	(1)
Conclusion	634	(1)
References	634	(9)
Alzheimer's Disease	643	(20)
R. Scott Turner
Introduction	643	(1)
Epidemiology	643	(1)
Clinical Criteria	644	(1)
Pathologic Criteria	644	(2)
Risk Factors	646	(1)
Genetics of Familial AD	647	(4)
Genetics of Sporadic (Late-Onset) Alzheimer's Disease	651	(1)
The Amyloid Hypothesis	652	(1)
Genetic Testing	653	(1)
Current Treatment Strategies	654	(1)
Future Treatment Strategies	655	(2)
Perspectives	657	(1)
References	658	(5)
Tauopathies	663	(30)
John C. van Swieten
Introduction	663	(1)
Tau Gene---Tau Protein	663	(2)
Frontotemporal Dementia	665	(1)
FTDP-17	666	(5)
Pathology of FTDP-17	671	(9)
Conclusions	680	(1)
References	681	(12)
Amyotrophic Lateral Sclerosis	693	(36)
Teepu Siddique
Lisa Dellefave
ALS Background	693	(10)
Approaches to Mendelian Inherited ALS	703	(3)
Understanding ALS Pathophysiology Through Mendelian Inherited ALS	706	(8)
Approaches to SALS as a Genetically Complex or Multifactorial Disorder	714	(3)
Clinical Management	717	(1)
Remaining Questions to Be Answered	718	(1)
References	719	(10)
Prion Diseases	729	(20)
William S. Baek
James A. Mastrianni
Introduction	729	(1)
Historical Background	729	(1)
Prion Protein (PrP) and the Prion Concept	730	(1)
Pathogenesis of Prions	731	(1)
Transmissible Properties of Prions	732	(1)
Epidemiology	733	(1)
Mutations of PRNP Cause Familial PrD	733	(2)
PRNP Polymorphisms	735	(1)
Prion-Like Protein Gene (Prnd)	736	(1)
The Phenotypes of PrD	737	(3)
Diagnosis of Prion Disease	740	(1)
Diagnostic Studies	741	(1)
Treatment	741	(1)
References	741	(8)
Index	749	(8)
About the Editor	757