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VCP mutations in familial and sporadic amyotrophic lateral sclerosis

Max Koppers1, Marka M van Blitterswijk, Lotte Vlam

  • 1Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.

Neurobiology of Aging
|November 15, 2011
PubMed

Insights

Valosin-containing protein (VCP) gene mutations are a rare cause of familial amyotrophic lateral sclerosis (ALS). This study found VCP mutations play a limited role in sporadic ALS and related disorders.

Area of Science:

  • Genetics
  • Neurology

Background:

  • Valosin-containing protein (VCP) gene mutations are linked to familial amyotrophic lateral sclerosis (ALS), inclusion body myopathy (IBM), Paget's disease of bone (PDB), and frontotemporal dementia (FTD).
  • The frequency of VCP mutations in sporadic ALS, sporadic ALS-FTD, and progressive muscular atrophy (PMA) remains unknown.

Purpose of the Study:

  • To investigate the prevalence and spectrum of VCP gene mutations in patients with familial ALS, sporadic ALS, sporadic ALS-FTD, and PMA.

Main Methods:

  • Genetic screening of VCP gene mutations in a cohort of 93 familial ALS, 754 sporadic ALS, 58 sporadic ALS-FTD, and 264 PMA patients.
  • Utilized conservation analysis and protein prediction software to assess mutation pathogenicity.

Main Results:

  • Identified two nonsynonymous VCP mutations: a known mutation (p.R159H) in a familial ALS patient with a family history of FTD, and a novel mutation (p.I114V) in a sporadic ALS patient.
  • The p.I114V mutation was predicted to be a rare benign polymorphism.

Conclusions:

  • VCP mutations are an infrequent cause of familial ALS.
  • The contribution of VCP mutations to sporadic ALS and related conditions appears minimal.

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