Identification of a novel missense mutation in Friedreich's ataxia –FXNW168R. Issue 4 (21st February 2019)

• Record Type: Journal Article
• Authors: Clark, Elisia; Strawser, Cassandra; Schadt, Kimberly; Lynch, David R.
• Is Part Of: Annals of clinical and translational neurology. Volume 6:Issue 4(2019)
• Page Start: 812
• Page End: 816
• Publication Date: 2019-02-21
• Subjects: Nervous system -- Diseases -- Periodicals; Neurology -- Periodicals; 616.8005
• DOI: 10.1002/acn3.728
• Languages: English
• ISSNs: 2328-9503

Abstract

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.