THE RELATIONSHIP BETWEEN TRINUCLEOTIDE (GAA) REPEAT LENGTH AND CLINICAL-FEATURES IN FRIEDREICH ATAXIA

Friedreich ataxia (FA) is associated with the expansion of a GAA trinu cleotide repeat in the first intron of the X25 gene. We found both all eles expanded in 67 FA patients from 48 Italian families. Five patient s from three families were compound heterozygotes with expansion on on e allele and an isoleucine-->phenylalanine change at position 154 on t he other one. We found neither expansions nor point mutations in three patients. The length of FA alleles ranged from 201 to 1,186 repeat un its, with no overlap with the normal range, and showed a negatively sk ewed distribution with a peak between 800 and 1,000 repeats. The FA re peat showed meiotic instability with a median variation of 150 repeats . The lengths of both larger and smaller alleles in each patient inver sely correlated with age at onset of the disorder. Smaller alleles sho wed the best correlation, accounting for similar to 50% of the variati on of age at onset. Mean allele length was significantly higher in pat ients with diabetes and in those with cardiomyopathy.