Multisystem Proteinopathy Due to <i>VCP</i> Mutations: A Review of Clinical Heterogeneity and Genetic Diagnosis
In this work, we review clinical features and genetic diagnosis of diseases caused by mutations in the gene encoding valosin-containing protein (VCP/p97), the functionally diverse AAA-ATPase. VCP is crucial to a multitude of cellular functions including protein quality control, stress granule format...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/13/6/963 |
| _version_ | 1797487163349139456 |
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| author | Gerald Pfeffer Grace Lee Carly S. Pontifex Roberto D. Fanganiello Allison Peck Conrad C. Weihl Virginia Kimonis |
| author_facet | Gerald Pfeffer Grace Lee Carly S. Pontifex Roberto D. Fanganiello Allison Peck Conrad C. Weihl Virginia Kimonis |
| author_sort | Gerald Pfeffer |
| collection | DOAJ |
| description | In this work, we review clinical features and genetic diagnosis of diseases caused by mutations in the gene encoding valosin-containing protein (VCP/p97), the functionally diverse AAA-ATPase. VCP is crucial to a multitude of cellular functions including protein quality control, stress granule formation and clearance, and genomic integrity functions, among others. Pathogenic mutations in <i>VCP</i> cause multisystem proteinopathy (VCP-MSP), an autosomal dominant, adult-onset disorder causing dysfunction in several tissue types. It can result in complex neurodegenerative conditions including inclusion body myopathy, frontotemporal dementia, amyotrophic lateral sclerosis, or combinations of these. There is also an association with other neurodegenerative phenotypes such as Alzheimer-type dementia and Parkinsonism. Non-neurological presentations include Paget disease of bone and may also include cardiac dysfunction. We provide a detailed discussion of genotype-phenotype correlations, recommendations for genetic diagnosis, and genetic counselling implications of VCP-MSP. |
| first_indexed | 2024-03-09T23:43:41Z |
| format | Article |
| id | doaj.art-437eea14c43348c3981e43cbaf8fbc62 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T23:43:41Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-437eea14c43348c3981e43cbaf8fbc622023-11-23T16:46:58ZengMDPI AGGenes2073-44252022-05-0113696310.3390/genes13060963Multisystem Proteinopathy Due to <i>VCP</i> Mutations: A Review of Clinical Heterogeneity and Genetic DiagnosisGerald Pfeffer0Grace Lee1Carly S. Pontifex2Roberto D. Fanganiello3Allison Peck4Conrad C. Weihl5Virginia Kimonis6Hotchkiss Brain Institute, Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, CanadaDivision of Genetic and Genomic Medicine, Department of Pediatrics, University of California Irvine Medical Center, Orange, CA 92868, USAHotchkiss Brain Institute, Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, CanadaOral Ecology Research Group, Faculty of Dental Medicine, Université Laval, Quebec City, QC G1V 0A6, CanadaCure VCP Disease, Inc., Americus, GA 31709, USADepartment of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USADivision of Genetic and Genomic Medicine, Department of Pediatrics, University of California Irvine Medical Center, Orange, CA 92868, USAIn this work, we review clinical features and genetic diagnosis of diseases caused by mutations in the gene encoding valosin-containing protein (VCP/p97), the functionally diverse AAA-ATPase. VCP is crucial to a multitude of cellular functions including protein quality control, stress granule formation and clearance, and genomic integrity functions, among others. Pathogenic mutations in <i>VCP</i> cause multisystem proteinopathy (VCP-MSP), an autosomal dominant, adult-onset disorder causing dysfunction in several tissue types. It can result in complex neurodegenerative conditions including inclusion body myopathy, frontotemporal dementia, amyotrophic lateral sclerosis, or combinations of these. There is also an association with other neurodegenerative phenotypes such as Alzheimer-type dementia and Parkinsonism. Non-neurological presentations include Paget disease of bone and may also include cardiac dysfunction. We provide a detailed discussion of genotype-phenotype correlations, recommendations for genetic diagnosis, and genetic counselling implications of VCP-MSP.https://www.mdpi.com/2073-4425/13/6/963VCPmultisystem proteinopathymyopathydementiaamyotrophic lateral sclerosisgenetics |
| spellingShingle | Gerald Pfeffer Grace Lee Carly S. Pontifex Roberto D. Fanganiello Allison Peck Conrad C. Weihl Virginia Kimonis Multisystem Proteinopathy Due to <i>VCP</i> Mutations: A Review of Clinical Heterogeneity and Genetic Diagnosis Genes VCP multisystem proteinopathy myopathy dementia amyotrophic lateral sclerosis genetics |
| title | Multisystem Proteinopathy Due to <i>VCP</i> Mutations: A Review of Clinical Heterogeneity and Genetic Diagnosis |
| title_full | Multisystem Proteinopathy Due to <i>VCP</i> Mutations: A Review of Clinical Heterogeneity and Genetic Diagnosis |
| title_fullStr | Multisystem Proteinopathy Due to <i>VCP</i> Mutations: A Review of Clinical Heterogeneity and Genetic Diagnosis |
| title_full_unstemmed | Multisystem Proteinopathy Due to <i>VCP</i> Mutations: A Review of Clinical Heterogeneity and Genetic Diagnosis |
| title_short | Multisystem Proteinopathy Due to <i>VCP</i> Mutations: A Review of Clinical Heterogeneity and Genetic Diagnosis |
| title_sort | multisystem proteinopathy due to i vcp i mutations a review of clinical heterogeneity and genetic diagnosis |
| topic | VCP multisystem proteinopathy myopathy dementia amyotrophic lateral sclerosis genetics |
| url | https://www.mdpi.com/2073-4425/13/6/963 |
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