VAPB and C9orf72 mutations in 1 familial amyotrophic lateral sclerosis patient

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• 作者：Marka van Blitterswijk ; Michael A. van Es ; Max Koppers ; Wouter van Rheenen ; Jelena Medic ; Helenius J. Schelhaas ; Anneke J. van der Kooi ; Marianne de Visser ; Jan H. Veldink ; Leonard H. van den Berg
• 关键词：Amyotrophic lateral sclerosis ; Motor neuron disease ; Familial ALS ; Genetics ; VAPB ; C9orf72
• 刊名：Neurobiology of Aging
• 出版年：2012
• 出版时间：December, 2012
• 年：2012
• 卷：33
• 期：12
• 页码：2950.e1-2950.e4
• 全文大小：382 K

文摘

Previously, we have reported amyotrophic lateral sclerosis (ALS) families with multiple mutations in major ALS-associated genes. These findings provided evidence for an oligogenic basis of ALS. In our present study, we screened a cohort of 755 sporadic ALS patients, 111 familial ALS patients (97 families), and 765 control subjects of Dutch descent for mutations in vesicle-associated membrane protein B (VAPB). We have identified 1 novel VAPB mutation (p.V234I) in a familial ALS patient known to have a chromosome 9 open reading frame 72 (C9orf72) repeat expansion. This p.V234I mutation was absent in control subjects, located in a region with high evolutionary conservation, and predicted to have damaging effects. Taken together, these findings provide additional evidence for an oligogenic basis of ALS.