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33 - Spinocerebellar ataxia type 8

from PART VIII - DOMINANTLY INHERITED PROGRESSIVE ATAXIAS

Published online by Cambridge University Press:  06 July 2010

Melinda L. Moseley
Affiliation:
Department of Genetics, Cell Biology, and Development, Institute of Human Genetics, University of innesota, Minneapolis, USA
Lawrence J. Schut
Affiliation:
Department of Neurology, Institute of Human Genetics
John W. Day
Affiliation:
Department of Neurology, CentraCare Clinic, St Cloud, Minnesota, USA
Laura P.W. Ranum
Affiliation:
Department of Genetics, Cell Biology, and Development, Institute of Human Genetics, University of innesota, Minneapolis, USA
Mario-Ubaldo Manto
Affiliation:
University of Brussels
Massimo Pandolfo
Affiliation:
Université de Montréal
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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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Publisher: Cambridge University Press
Print publication year: 2001

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  • Spinocerebellar ataxia type 8
    • By Melinda L. Moseley, Department of Genetics, Cell Biology, and Development, Institute of Human Genetics, University of innesota, Minneapolis, USA, Lawrence J. Schut, Department of Neurology, Institute of Human Genetics, John W. Day, Department of Neurology, CentraCare Clinic, St Cloud, Minnesota, USA, Laura P.W. Ranum, Department of Genetics, Cell Biology, and Development, Institute of Human Genetics, University of innesota, Minneapolis, USA
  • Edited by Mario-Ubaldo Manto, University of Brussels, Massimo Pandolfo, Université de Montréal
  • Book: The Cerebellum and its Disorders
  • Online publication: 06 July 2010
  • Chapter DOI: https://doi.org/10.1017/CBO9780511666469.035
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  • Spinocerebellar ataxia type 8
    • By Melinda L. Moseley, Department of Genetics, Cell Biology, and Development, Institute of Human Genetics, University of innesota, Minneapolis, USA, Lawrence J. Schut, Department of Neurology, Institute of Human Genetics, John W. Day, Department of Neurology, CentraCare Clinic, St Cloud, Minnesota, USA, Laura P.W. Ranum, Department of Genetics, Cell Biology, and Development, Institute of Human Genetics, University of innesota, Minneapolis, USA
  • Edited by Mario-Ubaldo Manto, University of Brussels, Massimo Pandolfo, Université de Montréal
  • Book: The Cerebellum and its Disorders
  • Online publication: 06 July 2010
  • Chapter DOI: https://doi.org/10.1017/CBO9780511666469.035
Available formats
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Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

  • Spinocerebellar ataxia type 8
    • By Melinda L. Moseley, Department of Genetics, Cell Biology, and Development, Institute of Human Genetics, University of innesota, Minneapolis, USA, Lawrence J. Schut, Department of Neurology, Institute of Human Genetics, John W. Day, Department of Neurology, CentraCare Clinic, St Cloud, Minnesota, USA, Laura P.W. Ranum, Department of Genetics, Cell Biology, and Development, Institute of Human Genetics, University of innesota, Minneapolis, USA
  • Edited by Mario-Ubaldo Manto, University of Brussels, Massimo Pandolfo, Université de Montréal
  • Book: The Cerebellum and its Disorders
  • Online publication: 06 July 2010
  • Chapter DOI: https://doi.org/10.1017/CBO9780511666469.035
Available formats
×