Book contents
- Frontmatter
- Contents
- List of contributors
- Preface
- Acknowledgments
- Foreword by Sid Gilman
- PART I INTRODUCTION
- PART II THEORIES OF CEREBELLAR CONTROL
- PART III CLINICAL SIGNS AND PATHOPHYSIOLOGICAL CORRELATIONS
- PART IV SPORADIC DISEASES
- PART V TOXIC AGENTS
- PART VI ADVANCES IN GRAFTS
- PART VII NEUROPATHOLOGY
- PART VIII DOMINANTLY INHERITED PROGRESSIVE ATAXIAS
- 26 Spinocerebellar ataxia type 1
- 27 Spinocerebellar ataxia type 2
- 28 Spinocerebellar ataxia type 3
- 29 Spinocerebellar ataxia type 4
- 30 Spinocerebellar ataxia type 5
- 31 Spinocerebellar ataxia type 6
- 32 Autosomal dominant cerebellar ataxia with progressive pigmentary macular dystrophy
- 33 Spinocerebellar ataxia type 8
- 34 Dentatorubral-pallidoluysian atrophy
- 35 Molecular mechanisms of triplet repeat expansions in ataxias
- PART IX RECESSIVE ATAXIAS
- Index
33 - Spinocerebellar ataxia type 8
from PART VIII - DOMINANTLY INHERITED PROGRESSIVE ATAXIAS
Published online by Cambridge University Press: 06 July 2010
- Frontmatter
- Contents
- List of contributors
- Preface
- Acknowledgments
- Foreword by Sid Gilman
- PART I INTRODUCTION
- PART II THEORIES OF CEREBELLAR CONTROL
- PART III CLINICAL SIGNS AND PATHOPHYSIOLOGICAL CORRELATIONS
- PART IV SPORADIC DISEASES
- PART V TOXIC AGENTS
- PART VI ADVANCES IN GRAFTS
- PART VII NEUROPATHOLOGY
- PART VIII DOMINANTLY INHERITED PROGRESSIVE ATAXIAS
- 26 Spinocerebellar ataxia type 1
- 27 Spinocerebellar ataxia type 2
- 28 Spinocerebellar ataxia type 3
- 29 Spinocerebellar ataxia type 4
- 30 Spinocerebellar ataxia type 5
- 31 Spinocerebellar ataxia type 6
- 32 Autosomal dominant cerebellar ataxia with progressive pigmentary macular dystrophy
- 33 Spinocerebellar ataxia type 8
- 34 Dentatorubral-pallidoluysian atrophy
- 35 Molecular mechanisms of triplet repeat expansions in ataxias
- PART IX RECESSIVE ATAXIAS
- Index
Summary
Introduction
It was recently demonstrated that an untranslated CTG expansion causes a novel form of ataxia – spinocerebellar ataxia type 8 (SCA8: Koob et al., 1999a). In addition to being the first example of a dominant SCA that is not caused by the expansion of a CAG repeat translated into a polyglutamine tract, the mutation underlying SCA8 shows marked intergenerational changes that are probably responsible for dramatically variable disease penetrance. The RAPID cloning method used to isolate the SCA8 CTG expansion and the clinical and genetic features of the disease are discussed below.
RAPID cloning
As part of a broader goal to understand better the various genetic causes of ataxia and to develop a resource to clone novel ataxia genes, an ataxia DNA collection has been established that now represents over 380 different ataxia kindreds with dominant, recessive, and sporadic forms of adult-onset ataxia (Moseley et al., 1998). Table 33.1 summarizes the inheritance patterns of the various families represented in the collection. Although direct gene tests are now available for eight of the ataxia loci, a large portion of the dominant ataxia families in our collection (∼35%) do not harbor expansions at the known loci, and thus remain genetically undefined.
To determine whether or not CAG repeat expansions are the pathogenic mechanism involved for some of these genetically undefined forms of ataxia, the repeat expansion detection (RED) assay was performed on affected family representatives. The RED assay, developed by Schalling et al. (1993), is an elegant technique that allows for the detection of potentially pathogenic trinucleotide repeat expansions without prior knowledge of chromosomal location.
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- The Cerebellum and its Disorders , pp. 469 - 480Publisher: Cambridge University PressPrint publication year: 2001