Spinocerebellar ataxia type 6: CAG repeat expansion in alpha1A voltage-dependent calcium channel gene and clinical variations in Japanese population

Ann Neurol. 1997 Dec;42(6):879-84. doi: 10.1002/ana.410420609.

Abstract

Autosomal dominant spinocerebellar ataxias (SCAs) are clinically and genetically a heterogeneous group of neurodegenerative disorders. Recently, mild CAG repeat expansion in the alpha1A voltage-dependent calcium channel gene has been found to be associated with a type of autosomal dominant SCA (SCA6). We analyzed 98 Japanese families with autosomal dominant SCAs, for whom CAG repeat expansions of the SCA1, SCA2, Machado-Joseph disease/SCA3, and dentatorubral-pallidoluysian atrophy genes were excluded, and 5 apparently sporadic cases of cortical cerebellar atrophy. The diagnosis of SCA6 was confirmed in 30 families (31%) comprising 47 affected individuals and 1 sporadic case. The size of expanded CAG repeats ranged from 21 to 26 repeat units and was found to be correlated inversely with age at onset. We identified 2 SCA6 patients homozygous for expanded CAG repeats, whose ages at onset were earlier than the 95% lower confidence level, suggesting the presence of a gene dosage effect of expanded CAG repeat. Ataxia is the most common initial symptom found in 45 of the 48 patients. Patients with a prolonged disease course showed other accompanying clinical features including dystonic postures, involuntary movements, and abnormalities in tendon reflexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Calcium Channels / genetics*
  • DNA Primers
  • Female
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Spinocerebellar Degenerations / ethnology
  • Spinocerebellar Degenerations / genetics*
  • Trinucleotide Repeats*

Substances

  • CACNA1A protein, human
  • Calcium Channels
  • DNA Primers