Identification of a novel missense mutation in Friedreich's ataxia –FXN(W) (168R)

Friedreich's ataxia, characterized by decreased expression of frataxin protein, is caused by GAA trinucleotide repeats within intron 1 in 98% of patients. Two percent of patients carry GAA repeats in conjunction with a point mutation. In this work, we find that frataxin(W168R), a novel disease‐causing missense mutation, is expressed predominantly as the intermediate frataxin(42‐210) form, with very little expression of mature frataxin(81‐210) form. Its localization to mitochondria is not impaired. Additionally, increasing frataxin(W168R) precursor levels do not lead to an increase in mature frataxin levels, suggesting these patients will require alternative approaches to repair frataxin processing in order to treat the disorder in a disease‐modifying manner.