title: VCP gene analyses in Japanese patients with sporadic amyotrophic lateral sclerosis identify a new mutation.
abstract: Accumulating evidence has proven that mutations in the VCP gene encoding valosin-containing protein (VCP) cause inclusion body myopathy with Paget disease of the bone and frontotemporal dementia. This gene was later found to be causative for amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, occurring typically in elderly persons. We thus sequenced the VCP gene in 75 Japanese patients with sporadic ALS negative for mutations in other genes causative for ALS and found a novel mutation, p.Arg487His, in 1 patient. The newly identified mutant as well as known mutants rendered neuronal cells susceptible to oxidative stress. The presence of the mutation in the Japanese population extends the geographic region for involvement of the VCP gene in sporadic ALS to East Asia.
authors.affiliation: Department of Neurology, Sakai Hospital, Kinki University Faculty of Medicine, Osaka, Japan; Department of Neurology, Kinki University Faculty of Medicine, Osaka, Japan. Electronic address: hirano_makito@yahoo.co.jp.
authors.forename: Makito
authors.initials: M
authors.lastname: Hirano
authors.affiliation: Department of Neurology, Sakai Hospital, Kinki University Faculty of Medicine, Osaka, Japan.
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Neurology, Kinki University Faculty of Medicine, Osaka, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Saigoh
authors.affiliation: Department of Neurology, Sakai Hospital, Kinki University Faculty of Medicine, Osaka, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Sakamoto
authors.affiliation: Department of Neurology, Sakai Hospital, Kinki University Faculty of Medicine, Osaka, Japan; Department of Neurology, Kinki University Faculty of Medicine, Osaka, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ueno
authors.affiliation: Department of Neurology, Sakai Hospital, Kinki University Faculty of Medicine, Osaka, Japan.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Isono
authors.affiliation: Department of Neurology, Kinki University Faculty of Medicine, Osaka, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Mitsui
authors.affiliation: Department of Neurology, Kinki University Faculty of Medicine, Osaka, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Kusunoki
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000473:pathology; D044466:Asian People / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D009447:Neuroblastoma / Q000473:pathology; D018384:Oxidative Stress / Q000235:genetics; D014407:Tumor Cells, Cultured; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein
keywords: Amyotrophic lateral sclerosis; Frontotemporal dementia; IBM; Inclusion body myopathy; Oxidative stress; Paget disease of bone