Journal article
Compound heterozygous FXN mutations and clinical outcome in friedreich ataxia
CA Galea, A Huq, PJ Lockhart, G Tai, LA Corben, EM Yiu, LC Gurrin, DR Lynch, S Gelbard, A Durr, F Pousset, M Parkinson, R Labrum, P Giunti, SL Perlman, MB Delatycki, MV Evans-Galea
Annals of Neurology | Published : 2016
DOI: 10.1002/ana.24595
Abstract
Objective Friedreich ataxia (FRDA) is an inherited neurodegenerative disease characterized by ataxia and cardiomyopathy. Homozygous GAA trinucleotide repeat expansions in the first intron of FXN occur in 96% of affected individuals and reduce frataxin expression. Remaining individuals are compound heterozygous for a GAA expansion and a FXN point/insertion/deletion mutation. We examined disease-causing mutations and the impact on frataxin structure/function and clinical outcome in FRDA. Methods We compared clinical information from 111 compound heterozygotes and 131 individuals with homozygous expansions. Frataxin mutations were examined using structural modeling, stability analyses and syste..
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Awarded by European Union Seventh Framework Program
Funding Acknowledgements
The authors are funded by the National Health and Medical Council of Australia (Project Grants to M.B.D., P.J.L., and M.V.E.G.; Career Development Fellowship to P.J.L.; Early Career Fellowships to L.A.C. and E.M.Y.), the Friedreich Ataxia Research Alliance USA, the Friedreich Ataxia Research Association Australasia, Multiple Sclerosis Research Australia (Incubator Grant to C.A.G.), the Victorian Government Operational Infrastructure Support Program, the European Union Seventh Framework Program (FP7/2007-2013; Grant 242193/EFACTS to P.G.), and the National Institute for Health Research University College London Hospitals Biomedical Research Center (to P.G.).