TY - JOUR
T1 - VCP mutations in familial and sporadic amyotrophic lateral sclerosis
AU - Koppers, Max
AU - van Blitterswijk, Marka M.
AU - Vlam, Lotte
AU - Rowicka, Paulina A.
AU - van Vught, Paul W.J.
AU - Groen, Ewout J.N.
AU - Spliet, Wim G.M.
AU - Engelen-Lee, Joo Yeon
AU - Schelhaas, Helenius J.
AU - de Visser, Marianne
AU - van der Kooi, Anneke J.
AU - van der Pol, W. Ludo
AU - Pasterkamp, R. Jeroen
AU - Veldink, Jan H.
AU - van den Berg, Leonard H.
N1 - Funding Information:
We thank all patients and healthy volunteers who participated in this project as well as the study staff, general practitioners, and pharmacists. This work has received funding from the European Community's Health Seventh Framework Programme ( FP7/2007-2013 ) under grant agreement 259867, VSB fonds, EURO-MOTOR FP7, The Netherlands ALS Foundation (JHV, and LHvdB), Neuroscience and Cognition Utrecht (NCU), the Prinses Beatrix Fonds (Kersten Foundation), and the Adessium Foundation (RJP, JHV, and LHvdB). J.H.V. is supported by the Brain Foundation of The Netherlands and J.H.V, R.J.P., and M.K. are supported by the Thierry Latran Foundation.
PY - 2012/4
Y1 - 2012/4
N2 - 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.
AB - 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.
KW - Amyotrophic lateral sclerosis
KW - Genetics
KW - Motor neuron disease
KW - Mutations
KW - Valosin-containing protein
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U2 - 10.1016/j.neurobiolaging.2011.10.006
DO - 10.1016/j.neurobiolaging.2011.10.006
M3 - Article
C2 - 22078486
AN - SCOPUS:84856958110
SN - 0197-4580
VL - 33
SP - 837.e7-837.e13
JO - Neurobiology of aging
JF - Neurobiology of aging
IS - 4
ER -