• Max Koppers, Marka M van Blitterswijk, Lotte Vlam, Paulina A Rowicka, Paul W J van Vught, Ewout J N Groen, Wim G M Spliet, JooYeon Engelen-Lee, Helenius J Schelhaas, Marianne de Visser, Anneke J van der Kooi, W-Ludo van der Pol, R Jeroen Pasterkamp, Jan H Veldink, and Leonard H van den Berg.
• Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
• Neurobiol. Aging. 2012 Apr 1;33(4):837.e7-13.

AbstractMutations 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.Copyright © 2012 Elsevier Inc. All rights reserved.

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