title: VAPB and C9orf72 mutations in 1 familial amyotrophic lateral sclerosis patient.
abstract: 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.
authors.affiliation: Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, The Netherlands.
authors.forename: Marka
authors.initials: M
authors.lastname: van Blitterswijk
authors.forename: Michael A
authors.initials: MA
authors.lastname: van Es
authors.forename: Max
authors.initials: M
authors.lastname: Koppers
authors.forename: Wouter
authors.initials: W
authors.lastname: van Rheenen
authors.forename: Jelena
authors.initials: J
authors.lastname: Medic
authors.forename: Helenius J
authors.initials: HJ
authors.lastname: Schelhaas
authors.forename: Anneke J
authors.initials: AJ
authors.lastname: van der Kooi
authors.forename: Marianne
authors.initials: M
authors.lastname: de Visser
authors.forename: Jan H
authors.initials: JH
authors.lastname: Veldink
authors.forename: Leonard H
authors.initials: LH
authors.lastname: van den Berg
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D000073885:C9orf72 Protein; D015331:Cohort Studies; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D033921:Vesicular Transport Proteins / Q000235:genetics*
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D011506:Proteins; C496748:VAPB protein, human; D033921:Vesicular Transport Proteins