title: Valosin-containing protein (VCP) mutations in sporadic amyotrophic lateral sclerosis.
abstract: We recently reported that mutations in the valosin-containing protein (VCP) gene are a cause of 1%-2% of familial amyotrophic lateral sclerosis (ALS) cases, but their role in the pathogenesis of sporadic ALS is unclear. We undertook mutational screening of VCP in 701 sporadic ALS cases. Three pathogenic variants (p.Arg159Cys, p.Asn387Thr, and p.R662C) were found in three U.S. cases, each of whom presented with progressive upper and lower motor neuron signs consistent with definite ALS by El Escorial diagnostic criteria. Our data indicate that VCP mutations may underlie apparently sporadic ALS but account for <1% of this form of disease.
authors.affiliation: Neuromuscular Diseases Research Unit, Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD 20892, USA.
authors.forename: Yevgeniya
authors.initials: Y
authors.lastname: Abramzon
authors.forename: Janel O
authors.initials: JO
authors.lastname: Johnson
authors.forename: Sonja W
authors.initials: SW
authors.lastname: Scholz
authors.forename: J P
authors.initials: JP
authors.lastname: Taylor
authors.forename: Maura
authors.initials: M
authors.lastname: Brunetti
authors.forename: Andrea
authors.initials: A
authors.lastname: Calvo
authors.forename: Jessica
authors.initials: J
authors.lastname: Mandrioli
authors.forename: Michael
authors.initials: M
authors.lastname: Benatar
authors.forename: Gabriele
authors.initials: G
authors.lastname: Mora
authors.forename: Gabriella
authors.initials: G
authors.lastname: Restagno
authors.forename: Adriano
authors.initials: A
authors.lastname: Chiò
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Traynor
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D018797:Cell Cycle Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D014481:United States; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein