Abstract
Two French-Canadian sibs with cerebellar ataxia and dysarthria were seen in our neurogenetics clinic. The older brother had global developmental delay and spastic paraplegia. Brain MRIs from these two affected individuals showed moderate to severe cerebellar atrophy. To identify the genetic basis for their disease, we conducted a whole exome sequencing (WES) investigation using genomic DNA prepared from the affected sibs and their healthy father. We identified two mutations in the SIL1 gene, which is reported to cause Marinesco-Sjögren syndrome. This study emphasizes how the diagnosis of patients with ataxic gait and cerebellar atrophy may benefit from WES to identify the genetic cause of their condition.
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Acknowledgments
We are grateful to the patients and their parents for their participation in this study. A.N. holds a Doctoral Award—Frederick Banting and Charles Best Graduate Scholarship by the Canadian Institutes of Health Research (CIHR) and a post-doctoral fellowship from the Fonds de Recherche du Québec en Santé (FRQS). R.L.P. received the Preston-Robb fellowship from the Montreal Neurological Institute and a doctoral scholarship from the Fonds de Recherche du Québec en Santé (FRQS). G.B. has received a Research Scholar Junior 1 award from the Fonds de Recherche du Québec en Santé (FRQS). G.A.R. holds a Canada Research Chair for the Genetics of Brain Diseases and is supported by the RMGA and the Canadian Institutes of Health Research. This work was selected for study by the FORGE Canada Steering Committee, consisting of K. Boycott (University of Ottawa), J. Friedman (University of British Columbia), J. Michaud (University of Montreal), F. Bernier (University of Calgary), M. Brudno (University of Toronto), B. Fernandez (Memorial University), B. Knoppers (McGill University), M. Samuels (University of Montreal), and S. Scherer (University of Toronto). We would also like to thank the McGill University and Genome Quebec Innovation Center.
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Noreau, A., La Piana, R., Marcoux, C. et al. Novel SIL1 mutations cause cerebellar ataxia and atrophy in a French-Canadian family. Neurogenetics 16, 315–318 (2015). https://doi.org/10.1007/s10048-015-0455-z
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DOI: https://doi.org/10.1007/s10048-015-0455-z