We report two large, unrelated families with spinocerebellar ataxia type 1 (SCA1) from the same village in the southeastern, mountain region of Serbia: Family 1 with 16, and Family 2 with nine affected members, identified in four consecutive generations. They significantly differ in the age at onset (31.8 ± 10.7 and 45.0 ± 8.4 years in Family 1 and Family 2, respectively; p<0.01), despite the lack of difference in the mean number of CAG trinucleotides in the ataxin-1 gene. Analysis of D6S337 haplotypes in SCA1-affected patients suggest that SCA1 expansions in these two families are not from the same origin. Similarity of the length of CAG repeat expansions in the ataxin-1 gene in these two unrelated families, as well as the similarity of environmental factors, suggests that some other, unknown genetic factor(s), could contribute to the variability of the age at onset of SCA1.

Key words: age at onset, ataxin?1 gene, SCA1, trinucleotides, environmental factor(s)