Spinocerebellar ataxia type 1

Huda Y. Zoghbi, Harry T. Orr

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disorder characterized by ataxia, dysarthria and progressive bulbar dysfunction. The SCA 1 gene which maps to the short arm of chromosome 6 has been isolated using a positional cloning approach. The SCA1 transcript is 10660 bases and encodes a novel protein, ataxin-1, with a predicted molecular weight of 87 kDa. Expansion of a CAG repeat localized near the amino terminus of ataxin-1 has been found to be the mutational mechanism in SCA1. This CAG repeat is highly polymorphic with normal alleles containing 6-39 repeats. Individuals affected with SCA1 have one normal allele and one expanded allele containing 40-81 repeats. The size of the repeat correlates inversely with the age of onset of symptoms and the severity of disease. The repeat is a continuous CAG repeat tract on SCA1 chromosomes whereas in ≥ 98% of normal alleles one or more CAT interruptions break the CAG repeat tracts into two tracts containing less than 18 repeats each. This suggests that loss of CAT interruptions within the SCA1 CAG repeat on normal chromosomes leads to triplet instability.

Original languageEnglish (US)
Pages (from-to)29-35
Number of pages7
JournalSeminars in Cell Biology
Volume6
Issue number1
DOIs
StatePublished - Feb 1995

Bibliographical note

Funding Information:
The authors thank Catherine Tasnier and Dr. Belinda Rossiter for preparation of the illustrations in this manuscript. This work was supported by grants from the National Institutes of Health and the Muscular Dystrophy Association.

Keywords

  • anticipation
  • glutamine
  • neurodegeneration
  • spinocerebellar ataxia
  • trinucleotide repeat

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