A survey of spinocerebellar ataxia in South Brazil – 66 new cases with Machado-Joseph disease, SCA7, SCA8, or unidentified disease–causing mutations
Background The autosomal dominant spinocerebellar ataxias (SCAs) are a clinical and genetically heterogeneous group of debilitating, neurodegenerative diseases, related to fourteen different loci– SCAs 1, 2, 4, 5, 6, 7, 8, 10, 11, 12, 13 and 14, Machado-Joseph disease (MJD/SCA 3), and DRPLA. Objectives (1) to verify the frequency of SCA1, SCA2, MJD, DRPLA, SCA6, SCA7 and SCA8 in a series of new SCA patients from South Brazil and (2) to compare their molecular and clinical characteristics with other patients previously described. Methods sixty-six cases were included in the present study: 52 were familial and 14 sporadic. Molecular analysis of the trinucleotide repeat loci were performed according to methods in the literature. Results 92 % of families with autosomal dominant inheritance segregated the MJD1 mutation, 2 % of families segregated the SCA7 mutation and 6 % remained undiagnosed. Among 14 isolated cases, one showed the SCA8 mutation. Clinical and molecular findings were similar to those already described in the literature, but revealed (1) one SCA7 patient with eyelid retraction, a sign usually related to MJD; and (2) one sporadic case of SCA8. Conclusions The proportion of MJD cases was very high, probably reflecting an Azorean founder effect. The estimated frequency of affected individuals with MJD, in our region, was 1.8 / 100,000, and of SCAs other than MJD, 0.2/100,000.
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