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
26 - Spinocerebellar ataxia type 1
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
Spinocerebellar ataxia type 1 (SCA1) is one of a complex group of autosomal dominant ataxias, which were first recognized as distinct from the recessive Friedreich's ataxia in 1893 by Marie. The clinicopathological presentations of these ataxias are extremely heterogeneous, with variable degrees of neurodegeneration in the cerebellum, spinal tracts, and brainstem. Thus, the classification of SCAs remained difficult and controversial until the 1990s, when the identification of distinct genes for several dominant ataxias allowed unequivocal genetic, if not clinical, differentiation (Orr and Zoghbi, 1996). SCA1 was one of the first neurogenetic diseases to be mapped to an autosome using classical linkage studies (Yakura et al., 1974; Jackson et al., 1977). The cloning of the SCA1 gene, the elucidation of a dynamic CAG trinucleotide repeat expansion as the mutational mechanism, and the establishment of cellular and animal models for this disorder have greatly advanced our understanding of the molecular and cellular mechanisms underlying SCA1 pathogenesis. These studies will undoubtedly provide the basis for developing effective therapeutics.
Clinical features
SCA1 usually strikes during the third or fourth decade of life, typically progressing over 10 to 15 years. In SCA1 families, the affected individuals in successive generations tend to have an earlier onset and more severe manifestations of the disease, a phenomenom referred to as anticipitation. Early onset in the first decade has been documented in such families (Schut, 1950; Zoghbi et al., 1988). The most salient clinical features of SCA1 include ataxia, dysarthria, and bulbar palsies. Other neurological abnormalities, such as extrapyramidal signs and peripheral neuropathy, often show extensive interfamilial and intrafamilial variability (Subramony and Vig, 1998; Zoghbi and Orr, 2000).
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- Information
- The Cerebellum and its Disorders , pp. 409 - 418Publisher: Cambridge University PressPrint publication year: 2001