FREQUENCY OF SPINOCEREBELLAR ATAXIA TYPE-1, DENTATORUBROPALLIDOLUYSIAN ATROPHY, AND MACHADO-JOSEPH DISEASE MUTATIONS IN A LARGE GROUP OF SPINOCEREBELLAR ATAXIA PATIENTS

The spinocerebellar ataxias (SCAs) are a heterogeneous group of neurod egenerative disorders varying in both clinical manifestations and mode of inheritance. Six different genes causing autosomal dominant SCA ar e mapped: SCAI, SCA2, Machado-Joseph disease (MJD)/SCA3, SCA4, SCA5, a nd dentatorubropallidoluysian atrophy (DRPLA). Expansions of an unstab le trinucleotide CAG repeat cause three of these disorders: SCA type 1 (SCA1), MJD, and DRPLA. We determined the frequency of the SCAI, DRPL A, and MJD mutations in a large group of unrelated SCA patients with v arious patterns of inheritance and different ethnic backgrounds. We st udied 92 unrelated SCA patients. The frequency of the SCAI mutation wa s 3% in the overall patient group and 10% in the non-Portuguese domina ntly inherited SCA subgroup. We found the DRPLA mutation in only one J apanese patient, who was previously diagnosed with this disease. We id entified the MJD mutation in 41% of the overall patient group, which i ncluded 38 autosomal dominant kindreds of Portuguese origin; the frequ ency of the MJD mutation among the non-Portuguese dominantly inherited cases was 17%. These results suggest that SCA may be occasionally cau sed by the SCAI mutation and rarely caused by the DRPLA mutation and t hat, to date, the MJD mutation seems to be the most common cause of do minantly inherited SCA. Finally, our results suggest that recessively inherited cases of SCA are not caused by the known trinucleotide repea t expansions.