Journal article

FXN methylation predicts expression and clinical outcome in Friedreich ataxia

Marguerite V Evans-Galea, Nissa Carrodus, Simone M Rowley, Louise A Corben, Geneieve Tai, Richard Saffery, John C Galati, Nicholas C Wong, Jeffrey M Craig, David R Lynch, Sean R Regner, Alicia FD Brocht, Susan L Perlman, Khalaf O Bushara, Christopher M Gomez, George R Wilmot, Lingli Li, Elizabeth Varley, Martin B Delatycki, Joseph P Sarsero

ANNALS OF NEUROLOGY | WILEY | Published : 2012


OBJECTIVE: Friedreich ataxia (FA) is the most common ataxia and results from an expanded GAA repeat in the first intron of FXN. This leads to epigenetic modifications and reduced frataxin. We investigated the relationships between genetic, epigenetic, and clinical parameters in a large case-control study of FA. METHODS: Clinical data and samples were obtained from individuals with FA during annual visits to our dedicated FA clinic. GAA expansions were evaluated by polymerase chain reaction (PCR) and restriction endonuclease digest. DNA methylation was measured using bisulfite-based EpiTYPER MassARRAY (Sequenom, San Diego, CA). FXN expression was determined using real-time reverse transcripta..

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Funding Acknowledgements

D.R.L., S. L. P., K.O.B., C. M. G., G. R. W., and M. B. D. are members of the Collaborative Clinical Research Network of Friedreich Ataxia (established and supported by the Friedreich Ataxia Research Alliance, USA).This study was supported by the National Health and Medical Council of Australia (Practitioner Fellowship to M. B. D.); the Friedreich Ataxia Research Alliance, USA (New Investigator Award to M.V.E.-G.); the Friedreich Ataxia Research Association, Australasia (M.V.E.-G., J.P.S and M. B. D.); the Australian Rotary Health Research Fund (M. V. E.-G., J.P.S and M. B. D.); the North Brighton Rotary Club (M. V. E.-G., J.P.S and M. B. D.); the Collier Charitable Fund of Australia (M. V. E.-G. and N.C.); the Victorian Government Operational Infrastructure Support Program; and the Muscular Dystrophy Association, USA (S.L.P.).D. R. L.: grants/grant pending, Santhera, Penwest/ENDO, Edison, MDA, NIH, FARA; patents, test for anti-NMDAR encephalitis; wife has served as a consultant for Biogen and Novartis (unrelated to present work). C. M. G.: grants/grants pending, speaking fees, travel expenses, Athena. M. B. D.: consultancy, Healthscope Pathology; grants/grants pending, National Health and Medical Research Council, FARA (USA), FARA (Australasia).