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. Received: 7 February 1997