Friedreich's disease: a real spectrum of clinical manifestations in terms of direct DNA-diagnosis

Friedreich's disease (FD) is autosomal-recessive form of hereditary ataxias conditioned by expansion of the trinucleotide GAA-repetitions in a new X25 gene. The study was performed in 20 patients from 13 families of different ethnic origin (Slavs, Turkmen, Moldavians, etc) with a suspicion to FD as well as in their 24 relatives who were clinically healthy. Direct DNA-diagn osis confirmed FD diagnosis in patients from 11 families; besides, a number of CAA-repetitions in the patients was in the range from 100 till 1200 (68 0+/-350). A molecular analysis revealed that FD severity was determined by a character of the mutation in each case: a classic form of the disease was characterized by the highest degree of the expansion of GAA-repetitions (m ore than 400), meanwhile atypic FD cases with late debute and slow progress ion were conditioned by either a small degree of the expansion of GAA-repet itions or by the presence of point mutations in one of the gene's alleles. A direct DNA-diagnosis permitted to determine a heterozygous carriage of th e mutation in 3 clinically healthy individuals. Such cases are necessary to take into consideration in medico-genetic consultations.