Novel p.Ile151Val mutation in VCP in a patient of African American descent with sporadic ALS
Open accessAbstract
The valosin containing protein (VCP) is a member of the AAA-ATPase family, a group of enzymatic molecular chaperones that have been associated with a range of cellular processes including ubiquitin-proteasome mediated degradation, membrane fusion, apoptosis, cell-cycle control, and autophagy.1 Mutations in VCP were first identified to cause familial inclusion body myopathy with early-onset Paget disease and frontotemporal dementia2 (IBMPFD) and more recently were found to be implicated in familial amyotrophic lateral sclerosis (ALS).3 It was suggested that VCP mutations may account for 1%–2% of familial ALS cases.3 Whether VCP mutations also contribute to sporadic ALS (SALS), however, has not yet been studied. Here, we report the identification of a novel p.Ile151Val mutation in VCP in a patient of African American descent with SALS. ### Case report. In the course of screening patients with ALS ascertained by the ALS Center at Mayo Clinic Florida (MCF) for mutations in the known ALS genes ( SOD1 , TARDBP , FUS , OPTN , and VCP ), we identified an African American patient with the c.451A>G mutation in exon 5 of VCP predicted to result in the p.Ile151Val substitution. Mutations were excluded in all other exons and genes analyzed in this patient. The VCP p.Ile151Val mutation was not previously reported in dbSNP or the 1000 Genomes databases and genotyping using a custom-designed ABI Taqman assay excluded this mutation from 407 healthy African American controls obtained from MCF (n = 317) and the Coriell Institute for Medical Research (n …
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VCP mutations are responsible for approximately 1-2% of familial ALS cases.
“but are also responsible for ~1-2% of familial ALS cases [241–243].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [241]
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- Authors
- DeJesus-Hernandez, M., Desaro, P., Johnston, A., Ross, O. A., Wszolek, Z. K., Ertekin-Taner, N., Graff-Radford, N. R., Rademakers, R., & Boylan, K.
- Affiliations
- From the Departments of Neuroscience (M.D.-H., O.A.R., N.E.-T., N.R.G.-R., R.R.) and Neurology (P.D., A.J., Z.K.W., N.E.-T., K.B.), Mayo Clinic, Jacksonville, FL.
- Mayo Clinic (US)
- Venue
- Neurology
- Published
- 2011-09-13
- Volume
- 77
- Issue
- 11
- Pages
- 1102-1103
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC3174069
- OpenAlex
- W2137138728
- Cited by
- 55
- References
- 5
- Citations by year
- 2024: 1 · 2023: 2 · 2022: 4 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 4 · 2017: 3 · 2016: 4 · 2015: 8 · 2014: 4 · 2013: 5 · 2012: 9
- FWCI
- 3.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Michael J. Fox Foundation for Parkinson's Research
- Mayo Clinic (KL2 RR024151, P50 AG016574)
- American Heart Association
- ALS Association
- Siragusa Foundation
- Pfizer
- Mayo Foundation for Medical Education and Research (AG016574)
- CurePSP
- Avanir Pharmaceuticals
- Cytokinetics
- Fondation pour la Recherche sur Alzheimer
- National Institutes of Health (AG016574)
- Forest Laboratories
- U.S. Public Health Service (R01 032990)
- Allergan
- Canadian Institutes of Health Research (P50 AG016574)
- National Institute on Aging (R01AG26251, AG016574, R01AG032990, R01AG026251, P50AG016574)
- National Institute of Neurological Disorders and Stroke (R01NS065782, P50NS072187)
- National Center for Research Resources (KL2RR024151)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Keywords
- VCP, sporadic ALS, novel mutations, African American patients, AAA+ ATPase, molecular chaperones
- MeSH terms
- Valosin Containing Protein, Adenosine Triphosphatases, Aged, Amino Acid Sequence, Amyotrophic Lateral Sclerosis, Black or African American, Female, Humans, Isoleucine, Molecular Sequence Data, Mutation, Valine, Fatal Outcome, Cell Cycle Proteins
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