MUTATIONS IN AMERICAN FAMILIES WITH SPINOCEREBELLAR ATAXIA (SCA) TYPE-3 - SCA3 IS ALLELIC TO MACHADO-JOSEPH DISEASE

We identified an expansion of the CAG trinucleotide repeat in the codi ng region of the Machado-Joseph disease gene in 7 of 24 American famil ies diagnosed with autosomal dominant ataxia. All affected individuals were heterozygous for an expanded allele that ranged from 67 to more than 200 CAG repeats, whereas the normal allele had 14 to 33 repeats. In contrast to the Azorean-Portuguese origins of Machado-Joseph diseas e, the two largest American families were of German and Dutch-African descent. Clinical, pathologic, and genetic evaluations suggest that Am erican families with spinocerebellar ataxia type 3 differ from those w ith Machado-Joseph disease by their ethnic origins, predominant spinop ontine atrophy, lack of dystonic features, and larger CAG repeat expan sion.