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 clin ical and genetically heterogeneous group of debilitating, neuro degenerativ e 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. Object ives (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 t heir molecular and clinical characteristics with other patients previously described. Methods sixty-six cases were included in the present study: 52 w ere familial and 14 sporadic. Molecular analysis of the trinucleotide repea t loci were performed according to methods in the literature. Results 92 % of families with autosomal dominant inheritance segregated the MJD I mutati on, 2 % of families segregated the SCA7 mutation and 6 % remained undiagnos ed. Among 14 isolated cases, one showed the SCA8 mutation. Clinical and mol ecular findings were similar to those already described in the literature, but revealed (1) one SCA7 patient with eyelid retraction, a sign usually re lated 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, w as 1.8 / 100,000, and of SCAs other than MJD, 0.2/100,000.