VCP gene analyses in Japanese patients with sporadic amyotrophic lateral sclerosis identify a new mutation

Neurobiol Aging. 2015 Mar;36(3):1604.e1-6. doi: 10.1016/j.neurobiolaging.2014.10.012. Epub 2014 Oct 16.

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.

Keywords: Amyotrophic lateral sclerosis; Frontotemporal dementia; IBM; Inclusion body myopathy; Oxidative stress; Paget disease of bone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / genetics*
  • Aged
  • Amyotrophic Lateral Sclerosis / genetics*
  • Amyotrophic Lateral Sclerosis / pathology
  • Asian People / genetics*
  • Cell Cycle Proteins / genetics*
  • Female
  • Genetic Association Studies*
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Male
  • Mutation / genetics*
  • Neuroblastoma / pathology
  • Oxidative Stress / genetics
  • Tumor Cells, Cultured
  • Valosin Containing Protein

Substances

  • Cell Cycle Proteins
  • Adenosine Triphosphatases
  • VCP protein, human
  • Valosin Containing Protein

Supplementary concepts

  • Amyotrophic lateral sclerosis 1