DETERMINANTS OF ONSET AGE IN FRIEDREICHS ATAXIA

We studied the factors that might influence onset age in Friedreich's ataxia in 41 cases (20 male, 21 female) homozygous for GAA expansion o n the first intron of X25 gene, Patients came from 18 multiplex famili es (13 couples, 5 triplets). Mean age (SD) was 18.1 (8.9) years and di d not differ by gender. Onset age and the sizes of the smaller (GAA1) and the larger (GAA2) allele in each pair showed high intrafamily corr elation. We found an inverse correlation between age at onset and GAA1 size, but not between age at onset and GAA2 size. Stepwise multiple r egression of onset age on GAA 1 size, sibling onset age, and GAA2 size showed that GAA1 accounts for 73% of onset age variance, and sibling onset age for an additional 13%. The study demonstrates that, in addit ion to GAA expansion size, other environmental or genetic familial fac tors influence disease expression.