title: VCP mutations in familial and sporadic amyotrophic lateral sclerosis.
abstract: Mutations in the valosin-containing protein (VCP) gene were recently reported to be the cause of 1%-2% of familial amyotrophic lateral sclerosis (ALS) cases. VCP mutations are known to cause inclusion body myopathy (IBM) with Paget's disease (PDB) and frontotemporal dementia (FTD). The presence of VCP mutations in patients with sporadic ALS, sporadic ALS-FTD, and progressive muscular atrophy (PMA), a known clinical mimic of inclusion body myopathy, is not known. To determine the identity and frequency of VCP mutations we screened a cohort of 93 familial ALS, 754 sporadic ALS, 58 sporadic ALS-FTD, and 264 progressive muscular atrophy patients for mutations in the VCP gene. Two nonsynonymous mutations were detected; 1 known mutation (p.R159H) in a patient with familial ALS with several family members suffering from FTD, and 1 mutation (p.I114V) in a patient with sporadic ALS. Conservation analysis and protein prediction software indicate the p.I114V mutation to be a rare benign polymorphism. VCP mutations are a rare cause of familial ALS. The role of VCP mutations in sporadic ALS, if present, appears limited.
authors.affiliation: Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Max
authors.initials: M
authors.lastname: Koppers
authors.forename: Marka M
authors.initials: MM
authors.lastname: van Blitterswijk
authors.forename: Lotte
authors.initials: L
authors.lastname: Vlam
authors.forename: Paulina A
authors.initials: PA
authors.lastname: Rowicka
authors.forename: Paul W J
authors.initials: PW
authors.lastname: van Vught
authors.forename: Ewout J N
authors.initials: EJ
authors.lastname: Groen
authors.forename: Wim G M
authors.initials: WG
authors.lastname: Spliet
authors.forename: JooYeon
authors.initials: J
authors.lastname: Engelen-Lee
authors.forename: Helenius J
authors.initials: HJ
authors.lastname: Schelhaas
authors.forename: Marianne
authors.initials: M
authors.lastname: de Visser
authors.forename: Anneke J
authors.initials: AJ
authors.lastname: van der Kooi
authors.forename: W-Ludo
authors.initials: WL
authors.lastname: van der Pol
authors.forename: R Jeroen
authors.initials: RJ
authors.lastname: Pasterkamp
authors.forename: Jan H
authors.initials: JH
authors.lastname: Veldink
authors.forename: Leonard H
authors.initials: LH
authors.lastname: van den Berg
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000690:Amyotrophic Lateral Sclerosis / Q000145:classification / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D019295:Computational Biology; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009426:Netherlands; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein