Analysis of Triplet Repeat Disorders

by Hayden; Michael

• ISBN13: 9781859962664
• ISBN10: 1859962661
• Edition: 1st
• Format: Nonspecific Binding
• Copyright: 1998-09-01
• Publisher: Garland Science

Summary

Using the clinical picture of these diseases as a starting point, the book reviews and integrates the current understanding of their molecular pathologies, the genotype-phenotype relationships, the mutational processes of trinucleotide repeats, and

Table of Contents

Contributors	ix
Abbreviations	xii
Preface	xiv
Foreword	xv
Introduction.	1	(12)
D.C. Rubinsztein
M.R. Hayden
Non-Mendelian inheritance	2	(1)
Trinucleotide repeat diseases -- overview	2	(8)
Conclusions	10	(1)
References	10	(3)
The FRAXA fragile site and fragile X syndrome.	13	(38)
E.E. Eichler
D.L. Nelson
Introduction	13	(1)
Clinical aspects	14	(4)
Historical aspects	18	(5)
The fragile X mutation	23	(9)
The FMRI gene	32	(7)
Summary	39	(1)
References	39	(12)
Molecular studies of the fragile sites FRAXE and FRAXF.	51	(10)
J.A. Skinner
G.S. Foss
W.J. Miller
K.E. Davies
Introduction	51	(1)
The FRAXE trinucleotide repeats	51	(1)
Expansion and transmission of the FRAXE trinucleotide repeat	52	(1)
Molecular diagnosis of FRAXE	53	(1)
Prevalence of FRAXE expansion	53	(1)
Clinical phenotype of FRAXE individuals	54	(1)
Patient management	55	(1)
Identification of the gene FMR2 associated with FRAXE	55	(1)
The FRAXF trinucleotide repeat	56	(2)
Summary	58	(1)
References	58	(3)
Myotonic dystrophy.	61	(24)
M. Hamshere
E. Newman
M. Alwazzan
J.D. Brook
Introduction	61	(1)
Epidemiology and prevelance	61	(1)
Clinical features	62	(3)
Evidence for anticipation	65	(1)
Identification of the gene	66	(1)
DMPK: normal function of the protein	67	(2)
The mutation genotype/phenotype relationship	69	(1)
Molecular phenotype of DM	70	(3)
Three models for the molecular mechanism of DM	73	(3)
Mouse models	76	(2)
References	78	(7)
Spinobulbar muscular atrophy.	85	(20)
L.K. Beitel
M.A. Trifiro
L. Pinsky
Introduction	85	(1)
Epidemiology and prevalence	86	(1)
Clinical features and natural history of SBMA	86	(3)
Laboratory features	89	(2)
Expression in carriers	91	(1)
Genetic features	91	(2)
Mutation and its relation to phenotype	93	(1)
Pathogenetic concepts	94	(4)
Management	98	(1)
Summary	98	(1)
References	99	(6)
Polyglutamine tract vs. protein context in SCA1 pathogenesis.	105	(14)
H.T. Orr
H.Y. Zoghbi
Introduction	105	(1)
Cellular localization studies of wild-type and mutant ataxin-1	106	(1)
Ataxin-1 interacting proteins	107	(2)
SCA1 transgenic mice develop a progressive neurological disease	109	(4)
The importance of protein context in SCA1 pathogenesis	113	(2)
References	115	(4)
Spinocerebellar ataxia type 2 (SCA2).	119	(10)
S.-M. Pulst
Epidemiology	119	(1)
Identification of the SCA2 gene	119	(1)
cDNA sequence	120	(7)
References	127	(2)
Spinocerebellar ataxia type 3/Machado-Joseph disease.	129	(16)
H.L. Paulson
History of SCA3/MJD: two names one disease	129	(2)
Clinical features	131	(1)
Pathological features	131	(4)
Molecular genetics of disease	135	(4)
Molecular mechanism of degeneration	139	(2)
References	141	(4)
Spinocerebellar ataxia type 6 (SCA6).	145	(10)
Cheng Chi Lee
Introduction	145	(1)
The human α voltage-dependent Ca2+ channel	146	(1)
Allelic disorders of spinocerebellar ataxia type 6 (SCA6)	147	(1)
Clinical and pathological findings in SCA6 patients	148	(1)
Ethnic frequency, age-of-onset and CAG repeat length	149	(1)
Clinical anticipation and transmission stability of expanded SCA6 allele	150	(1)
Summary	150	(1)
References	151	(4)
Spinocerebellar ataxia type 7 (SCA7).	155	(14)
G. Stevanin
G. David
N. Abbas
A. Durr
M. Holmberg
C. Duyckaerts
P. Giunti
G. Cancel
M. Ruberg
J.-L. Mandel
A. Brice
Introduction	155	(1)
Clinical and neuropathological features	155	(2)
Genetics and epidemiology	157	(1)
Identification of the SCA7 gene and the unstable mutation	158	(1)
Analysis of the CAG repeat sequence	159	(2)
Phenotype-genotype correlations	161	(1)
Intermediate alleles and new mutations to SCA7	162	(2)
Pathophysiology of SCA7	164	(1)
Summary	165	(1)
References	166	(3)
Huntington's Disease.	169	(40)
C.A. Ross
M.R. Hayden
Clinical features of Huntington's disease	169	(2)
The genetic aetiology of HD	171	(1)
Diagnosis of HD	172	(1)
The genetics of HD	173	(6)
Pathology of HD	179	(2)
Targeted gene deletions: insights into the role of the normal gene	181	(1)
Biochemistry and cell biology	182	(1)
Interacting proteins	183	(1)
Neurotoxicity	184	(1)
Polyglutamine	185	(1)
In vitro studies to understand the pathogenesis of HD	185	(3)
Transgenic animal models	188	(1)
Studies of human post-mortem brains	189	(1)
A model connecting aggregates and cell death	190	(1)
References	191	(18)
Dentatorubral-pallidoluysian atrophy (DRLPA).	209	(10)
S. Tsuji
Introduction	209	(1)
Molecular genetics of DRPLA	210	(1)
Clinical features of DRPLA and the genotype-phenotype correlation	211	(2)
Molecular basis of genetic anticipation	213	(1)
Mechanisms of neurodegeneration caused by CAG repeat expansion	213	(2)
References	215	(4)
Friedreich's ataxia.	219	(20)
M. Koenig
Introduction and history	219	(1)
Clincal aspects	219	(4)
Identification of the Friedriech's ataxia gene	223	(3)
Analysis of the GAA trinucleotide expansion	226	(4)
A mitochondrial function for frataxin	230	(3)
Conclusions	233	(1)
References	234	(5)
Anticipation, triplet repeats and psychiatric disorders.	239	(18)
M.G. McInnis
R. L. Margolis
Introduction	239	(1)
Psychiatric disorders and anticipation	240	(4)
Does anticipation in psychiatric disorders derive from trinucleotide repeat expansions?	244	(4)
Conclusion	248	(1)
References	249	(8)
Trinucleotide repeat mutation processes.	257	(12)
D.C. Rubinsztein
B. Amos
Introduction	257	(1)
General principles, features of microsatellite mutations	257	(4)
Mutations at triplet repeat disease loci	261	(3)
Conclusions	264	(1)
References	265	(4)
Diagnostic testing for trinucleotide repeat diseases.	269	(36)
B.W. Popovich
F. Quan
Introduction	269	(1)
Diagnostic techniques	270	(2)
An overview of testing strategies	272	(1)
Fragile X syndrome	273	(4)
FRAXE mental retardation 1	277	(1)
Myotonic dystrophy	278	(2)
Autosomal dominant cerebellar ataxias	280	(5)
Dentatorubralpallidoluysion atrophy	285	(1)
Huntington's disease	286	(3)
Spinal bulbar muscular atrophy	289	(1)
Friedreich's ataxia	290	(1)
Summary	291	(1)
References	292	(13)
Predictive testing for trinucleotide repeat disorders.	305	(20)
D. Craufurd
Introduction	305	(1)
Predictive testing by linkage analysis	306	(1)
Direct testing	306	(1)
Practical consequences	307	(1)
The psychological impact of predictive testing	308	(2)
Impact on family	310	(1)
Uptake of predictive testing	311	(2)
Guidelines for genetic counselling	313	(2)
Relevance of predictive test guidelines for diagnostic testing	315	(1)
Prenatal testing	316	(2)
Testing for other trinucleotide repeat disorders	318	(2)
References	320	(5)
Index	325