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 first intron of the frataxin gene on chromosome 9. We investigated the mosaicism of expanded alleles to elucidate the basis for genotype phenotype correlations. PATIENTS AND METHODS: We studied the instability of the GAA repeat in blood leukocytes from 45 individuals including 20 FRDA patients and 20 non-affected controls using small pool PCR combined with Southern blotting and hybridization. RESULTS: Expanded GAA repeats could be resolved into distinct alleles showing differences in length up to 1,000 triplets for an individual genome. We found a significant correlation between the size of the largest allele and the range of mosaicism. CONCLUSION: The somatic mosaicism for expanded repeats observed in FRDA patients rendered the precise measurement of allele sizes more difficult and may influence the results of studies correlating the clinical spectrum with the genotype. Following, a confidential prediction of the prognosis deduced from the repeat length is hardly possible for an individual FRDA patient.