VCP mutations in familial and sporadic amyotrophic lateral sclerosis

Max Koppers, Marka M. van Blitterswijk, Lotte Vlam, Paulina A. Rowicka, Paul W.J. van Vught, Ewout J.N. Groen, Wim G.M. Spliet, Joo Yeon Engelen-Lee, Helenius J. Schelhaas, Marianne de Visser, Anneke J. van der Kooi, W. Ludo van der Pol, R. Jeroen Pasterkamp, Jan H. Veldink, Leonard H. van den Berg

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)837.e7-837.e13
JournalNeurobiology of aging
Issue number4
StatePublished - Apr 2012


  • Amyotrophic lateral sclerosis
  • Genetics
  • Motor neuron disease
  • Mutations
  • Valosin-containing protein

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology


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