Journal article
An intronic GAA repeat expansion in FGF14 causes the autosomal-dominant adult-onset ataxia SCA50/ATX-FGF14
H Rafehi, J Read, DJ Szmulewicz, KC Davies, P Snell, LG Fearnley, L Scott, M Thomsen, G Gillies, K Pope, MF Bennett, JE Munro, KJ Ngo, L Chen, MJ Wallis, EG Butler, KR Kumar, KH Wu, SE Tomlinson, S Tisch Show all
American Journal of Human Genetics | Published : 2023
Abstract
Adult-onset cerebellar ataxias are a group of neurodegenerative conditions that challenge both genetic discovery and molecular diagnosis. In this study, we identified an intronic (GAA) repeat expansion in fibroblast growth factor 14 (FGF14). Genetic analysis of 95 Australian individuals with adult-onset ataxia identified four (4.2%) with (GAA)>300 and a further nine individuals with (GAA)>250. PCR and long-read sequence analysis revealed these were pure (GAA) repeats. In comparison, no control subjects had (GAA)>300 and only 2/311 control individuals (0.6%) had a pure (GAA)>250. In a German validation cohort, 9/104 (8.7%) of affected individuals had (GAA)>335 and a further six had (GAA)>250,..
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Awarded by Murdoch Children's Research Institute
Funding Acknowledgements
This work was supported by the Australian Government National Health and Medical Research Council grants (GNT2001513 and MRFF2007677) to P.J.L., M.B.D., and H.R. H.R. was supported by an NHMRC Emerging Leadership 1 grant (1194364) and M.B. was supported by an NHMRC Leadership 1 grant (1195236). Additional funding was provided by the Independent Research Institute Infrastructure Support Scheme, the Victorian State Government Operational Infrastructure Program and the Murdoch Children's Research Institute. N.B. and K.L. are supported by research grants from the Deutsche Forschungsgemeinschaft (DFG, FOR 2488). We would like to thank Frauke Hinrichs for technical support and Christoph Helmchen, Max Borsche, and Meike Kasten for help with the recruitment of the German participants.