ABSTRACT
Friedreich’s ataxia (FRDA) is a neurodegenerative disease caused by deficiency of frataxin, a protein finally identified in 1996 after years of attempts to find the FRDA gene. In the vast majority of patients (96-98%), defective expression of frataxin is due to a homozygous GAA triplet repeat expansion within the first intron of the FXN gene, located on chromosome 9q13 (Campuzano et al. 1996). Anomalous expansion of GAA repeats determines the formation of a triple helix non-B DNA structure, resulting in inhibition of frataxin mRNA transcription (Sakamoto et al. 2001). A small percentage of FRDA patients (approximately 2-4%) are compound heterozygotes with missense mutations in the gene (Cossée et al. 1999). They carry intronic GAA expansions on one allele and a point mutation, which is mainly located in the conserved C-terminal region of frataxin, within exons of the other allele.
