Differential stability of the (GAA)(n) tract in the Friedreich ataxia (STM7) gene

Friedreich ataxia (FA) is an autosomal recessive. neurodegenerative disorder characterized by polypurine trinucleotide expansion. The (GAA)(n) motif is located in intron 18 of the STM7 gene (previously considered as intron 1 of the X25 gene) on chromosome 9q13. We studied the distribution profile of the polymorphic (GAA)(n) repetitive tract in 178 healthy individuals. The number of repeats of the trinucleotide block ranged from 7 to 29. In three individuals there were more than 29 repetitions of the GAA motif. While two of the individuals would be diagnosed as carriers of the FA mutation (GAA size > 90), the status of the third person, with a (GAA)(58) tract. appears less clear at present. Thus an FA carrier rate of 1/60 to 1/90 can be assumed for the German population. In addition an intermediate-sized allele, (GAA)(38) was identified in a mother with two affected children. The (GAA)(38) allele appears to be expanded during transmission to at least (GAA)(66) and (GAA)(> 400) in her two FA-affected offspring. Therefore the shortest known STM7 allele conferring FA is (GAA)(66). These novel facts have to be considered for differential diagnosis and definition of the FA carrier state.