Limited somatic mosaicism for Friedreich's ataxia GAA triplet repeat expansions identified by small pool PCR in blood leukocytes

Objectives - Friedreich's ataxia (FRDA), the most common inherited ataxia, is associated with an unstable expansion of GAA repeats in the fn-st intron of the frataxin gene on chromosome 9. We investigated the mosaicism of exp anded alleles to elucidate the basis for genotype-phenotype correlations. P atients and methods - We studied the instability of the GAA repeat in blood leukocytes from 45 individuals including 20 FRDA patients and 20 non-affec ted controls using small pool PCR combined with Southern blotting and hybri dization. Results - Expanded GAA repeats could be resolved into distinct al leles showing differences in length up to 1000 triplets for an individual g enome. We found a significant correlation between the size of the largest a llele and the range of mosaicism. Conclusion - The somatic mosaicism for ex panded repeats observed in FRDA patients rendered the precise measurement o f allele sizes more difficult and may influence the results of studies corr elating the clinical spectrum with the genotype. Following, a confidential prediction of the prognosis deduced from the repeat length is hardly possib le for an individual FRDA patient.