Long-Term Experience in the Molecular Genetic Diagnosis of Friedreich Ataxia in the Russian Federation

Background/Objectives: Friedreich’s ataxia in considered the most common form of autosomal recessive ataxia; however, it’s prevalence in the Russian Federation remains poorly studied. Methods: The study included 974 patient samples referred for analysis of the expanded GAA repeat in intron 1 of the FXN gene, as well as 319 healthy individuals participating in a biomaterial donation program for IVF, using PCR-AFLP and fragment analysis with labeled primers. Sanger sequencing of the FXN gene was additionally performed for six patients who exhibited a heterozygous expanded allele. Results: The diagnosis of FRDA was confirmed in 142 patients: 139 of them had homozygous GAA repeat expansions, the most common mutation type in this disorder, while in 3 cases a heterozygous expansion was associated with a pathogenic point mutation in the FXN gene on the second allele. For 28 probands, biallelic GAA expansions in FXN were subsequently confirmed in their affected relatives. Among the 319 healthy donors, only 2 carriers of a pathogenic expansion were identified. Conclusions: This paper presents the results of a long-term study on the molecular genetic causes of FRDA in Russian Federation, yielding an estimated frequency of 1:102,000 individuals for the disease associated with GAA repeat expansion.