Molecular features of the CAG repeats of spinocerebellar ataxia 6 (SCA6)

Department of General Internal Medicine, Hiroshima University, Hirosima, Hiroshima, Japan
Human Molecular Genetics (Impact Factor: 6.68). 08/1997; 6(8):1283-7. DOI: 10.1093/hmg/6.8.1283
Source: PubMed

ABSTRACT Spinocerebellar ataxia 6 (SCA6) is an autosomal dominant spinocerebellar degeneration caused by the expansion of the polymorphic CAG repeat in the human alpha1A voltage-dependent calcium channel subunit gene (CACNL1A4 gene). We have analyzed 60 SCA6 individuals from 39 independent SCA6 Japanese families and found that the CAG repeat length is inversely correlated with the age of onset (n = 58, r = -0.51, P < 0.0001). SCA6 chromosomes contained 21-30 repeat units, whereas normal chromosomes displayed 6-17 repeats. There was no overlap between the normal and affected CAG repeat number. The anticipation of the disease was observed clinically in all eight parent-child pairs that we examined; the mean age of onset was significantly lower (P = 0.0042) in children than in parents. However, a parent-child analysis showed the increase in the expansion of CAG repeats only in one pair and no diminution in any affected cases. This result suggests that factors other than CAG repeats may produce the clinical anticipation. A homozygotic case could not demonstrate an unequivocal gene dosage effect on the age of onset.

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    • "SCA3 Standard PCR Kawaguchi et al., 1994 160bp þ 3n (n ¼ number of CAG repeats). SCA6 Standard PCR Matsuyama et al., 1997 102bp þ 3n (n ¼ number of CAG repeats). SCA7 Standard PCR David et al., 1997 272bp þ 3n (n ¼ number of CAG repeats). "
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    • "SCA6 is characterized by late-onset slow-progressive cerebellar ataxia and Purkinje ceUpredominant degeneration in the cerebellum (Sasaki et al., 1998) and appears to be more frequent in Japmese populations (Takano et al., 1998). Interestingly enough, a polymorphic CAG repeat was identified in the human Cav2.1 a,-subunit (Matsuyama et al., 1997; Zhuchenko et al., 1997), providing the molecular basis for this disorder. Expansion of CAG repeats encoding polyglutamine (polyQ) tracts has been linked to severa1 neurodegenerative diseases, including Huntington's disease and other fonns of spinocerebellar ataxia. "
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