Ethnic differences in the expression of neurodegenerative disease: Machado-Joseph disease in Africans and Caucasians

We describe several families of African origin with SCA3/Machado‐Joseph disease gene expansions. In these cases, the phenotype ranges from ataxia with parkinsonian signs to a syndrome clinically almost indistinguishable from idiopathic, L‐dopa–responsive Parkinson's disease. In contrast, these parkinsonian phenotypes are rare in those of European descent. Haplotype analysis shows that these African families do not share a common founder, thus a cis‐acting element in the promoter is unlikely to be responsible these unusual presentations. We suggest that trans‐acting factors are responsible for the variable phenotype and discuss the implications of diseases showing racially different expressivities. © 2002 Movement Disorder Society