AI Article Synopsis
- Friedreich ataxia (FA) is a genetic disorder caused by expansions of the (GAA)n trinucleotide repeat in the STM7 gene, primarily affecting neurological function.
- In a study of 178 healthy individuals, the number of GAA repeats varied, with some individuals exceeding the typical range, indicating they may be carriers of the FA mutation.
- The findings suggest a carrier rate of approximately 1 in 60 to 1 in 90 in the German population, and they also highlight the need to reassess definitions of the FA carrier status based on new observations of repeat expansions.
Article Abstract
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.
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