A Mutation in the Golgi Qb-SNARE Gene GOSR2 Causes Progressive Myoclonus Epilepsy with Early Ataxia
Mark A Corbett, Michael Schwake, Melanie Bahlo, Leanne M Dibbens, Meng Lin, Luke C Gandolfo, Danya F Vears, John D O'Sullivan, Thomas Robertson, Marta A Bayly, Alison E Gardner, Annemarie M Vlaar, G Christoph Korenke, Bastiaan R Bloem, Irenaeus F de Coo, Judith MA Verhagen, Anna-Elina Lehesjoki, Jozef Gecz, Samuel F Berkovic
AMERICAN JOURNAL OF HUMAN GENETICS | CELL PRESS | Published : 2011
The progressive myoclonus epilepsies (PMEs) are a group of predominantly recessive disorders that present with action myoclonus, tonic-clonic seizures, and progressive neurological decline. Many PMEs have similar clinical presentations yet are genetically heterogeneous, making accurate diagnosis difficult. A locus for PME was mapped in a consanguineous family with a single affected individual to chromosome 17q21. An identical-by-descent, homozygous mutation in GOSR2 (c.430G>T, p.Gly144Trp), a Golgi vesicle transport gene, was identified in this patient and in four apparently unrelated individuals. A comparison of the phenotypes in these patients defined a clinically distinct PME syndrome cha..View full abstract
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We are grateful for the cooperation of the families involved in this study. Thank you to Maike Langer, Thomas Hoefken, Lisa van Winsen, Maria Digenis, Bev Johns, and Rob King for excellent technical assistance; Paul Saftig for valuable advice; and Johannes Aerts for kindly providing us with the anti-human beta-GC antibody 8E4. M.B. and J.G. were supported by the National Health and Medical Research Council (NH&MRC) with a Career Development Award and a Principal Research Fellowship, respectively. This project was supported by NH&MRC program grant 400121 and by the Research Training Group (GRK1459), funded by the Deutsche Forschungsgemeinschaft (DFG) to P.S. and M.S. The study was approved by the Austin Health Human Research Ethics Committee and informed consent was obtained from all participants.