Deep Intronic <i>FGF14</i> GAA Repeat Expansion in Late-Onset Cerebellar Ataxia
David Pellerin, Matt C. Danzi, Carlo Wilke, M. Renaud, Sarah Fazal, Marie‐Josée Dicaire, Carolin K. Scriba, Catherine Ashton, Christopher Yanick, Danique Beijer, Adriana Rebelo, Clarissa Rocca, Zane Jaunmuktane, Joshua A. Sonnen, Roxanne Larivière, David Genı́s, Laura Molina‐Porcel, Karine Choquet, Rawan Sakalla, Sylvie Provost, Rebecca Robertson, Xavier Allard‐Chamard, Martine Tétreault, Sarah J. Reiling, Sara Nagy, Vikas Nishadham, Meera Purushottam, Seena Vengalil, Mainak Bardhan, Atchayaram Nalini, Zhongbo Chen, Jean Mathieu, Rami Massie, Colin Chalk, Anne‐Louise Lafontaine, François Evoy, Marie‐France Rioux, Jiannis Ragoussis, Kym M. Boycott, Marie‐Pierre Dubé, Antoine Duquette, Henry Houlden, Gianina Ravenscroft, Nigel G. Laing, Phillipa J. Lamont, Mario Saporta, Rebecca Schüle, Lüdger Schöls, Roberta La Piana, Matthis Synofzik, Stephan Züchner, Bernard Brais
Abstract
BACKGROUND: The late-onset cerebellar ataxias (LOCAs) have largely resisted molecular diagnosis. METHODS: We sequenced the genomes of six persons with autosomal dominant LOCA who were members of three French Canadian families and identified a candidate pathogenic repeat expansion. We then tested for association between the repeat expansion and disease in two independent case-control series - one French Canadian (66 patients and 209 controls) and the other German (228 patients and 199 controls). We also genotyped the repeat in 20 Australian and 31 Indian index patients. We assayed gene and protein expression in two postmortem cerebellum specimens and two induced pluripotent stem-cell (iPSC)-derived motor-neuron cell lines. RESULTS: RNA and protein. CONCLUSIONS: was found to be associated with LOCA. (Funded by Fondation Groupe Monaco and others.).