Atypical Friedreich ataxia phenotype associated with a novel missense mutation in the X25 gene

We describe two sisters with early onset gait ataxia, rapid disease progres sion, absent or very mild dysarthria and upper limb dysmetria, retained kne e jerks in one, slight to moderate peripheral nerve involvement, and diabet es. Molecular analysis showed that they are compound heterozygotes for GAA expansion and a novel exon 5a missense mutation (R165P). This mutation appe ars to be associated with an atypical but not milder Friedreich ataxia phen otype.