DNA diagnostics of Friedreich's ataxia

Friedreich's ataxia (FA) is an autosomal recessive neurodegenerative disease with an estimated prevalence of 1:50 000-100 000. The corresponding gene (X25) is mapped on chromosome 9q13 encoding a 210-amino acid protein, named frataxin, with unknown function. In 98 Sib of FA patients a dynamic mutation is found. The mutation is characterized by amplification of GAA triplet repeats within intron 1 of X25 gene. We used the PCR method for detection of the amplified GAA region in 16 patients with the clinical diagnosis of Fk For visualisation of amplified repeats we used agarose gel and for radioactive labeled products denaturating PAGE. From 16 patients we detected amplifications of GAA trinucleotides in 7 probands. Twenty-two healthy carriers were found in their families. There were from 400 to 900 GAA trinucleotides. In one case an equal number of 447 amplified sequences was detected on both alleles. In all families the number of amplified GAA repeats, through the pedigree, was stable in length. Identification of X25 gene and molecular genetic diagnosis of this disorder is a marked contribution to the neurology and clinical genetics. It offers the real possibility of classification of this type of ataxia and the subsequent genetic counselling, possibly reevaluation of clinical results.