Identification of a novel missense mutation in Friedreich's ataxia –FXNW168R

Abstract

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.

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