Cargando…

Multisystem Proteinopathy Due to VCP 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...

Descripción completa

Detalles Bibliográficos
Autores principales: Pfeffer, Gerald, Lee, Grace, Pontifex, Carly S., Fanganiello, Roberto D., Peck, Allison, Weihl, Conrad C., Kimonis, Virginia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9222868/
https://www.ncbi.nlm.nih.gov/pubmed/35741724
http://dx.doi.org/10.3390/genes13060963
_version_ 1784732980202176512
author Pfeffer, Gerald
Lee, Grace
Pontifex, Carly S.
Fanganiello, Roberto D.
Peck, Allison
Weihl, Conrad C.
Kimonis, Virginia
author_facet Pfeffer, Gerald
Lee, Grace
Pontifex, Carly S.
Fanganiello, Roberto D.
Peck, Allison
Weihl, Conrad C.
Kimonis, Virginia
author_sort Pfeffer, Gerald
collection PubMed
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 VCP 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.
format Online
Article
Text
id pubmed-9222868
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-92228682022-06-24 Multisystem Proteinopathy Due to VCP Mutations: A Review of Clinical Heterogeneity and Genetic Diagnosis Pfeffer, Gerald Lee, Grace Pontifex, Carly S. Fanganiello, Roberto D. Peck, Allison Weihl, Conrad C. Kimonis, Virginia Genes (Basel) Review 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 VCP 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. MDPI 2022-05-27 /pmc/articles/PMC9222868/ /pubmed/35741724 http://dx.doi.org/10.3390/genes13060963 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Pfeffer, Gerald
Lee, Grace
Pontifex, Carly S.
Fanganiello, Roberto D.
Peck, Allison
Weihl, Conrad C.
Kimonis, Virginia
Multisystem Proteinopathy Due to VCP Mutations: A Review of Clinical Heterogeneity and Genetic Diagnosis
title Multisystem Proteinopathy Due to VCP Mutations: A Review of Clinical Heterogeneity and Genetic Diagnosis
title_full Multisystem Proteinopathy Due to VCP Mutations: A Review of Clinical Heterogeneity and Genetic Diagnosis
title_fullStr Multisystem Proteinopathy Due to VCP Mutations: A Review of Clinical Heterogeneity and Genetic Diagnosis
title_full_unstemmed Multisystem Proteinopathy Due to VCP Mutations: A Review of Clinical Heterogeneity and Genetic Diagnosis
title_short Multisystem Proteinopathy Due to VCP Mutations: A Review of Clinical Heterogeneity and Genetic Diagnosis
title_sort multisystem proteinopathy due to vcp mutations: a review of clinical heterogeneity and genetic diagnosis
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9222868/
https://www.ncbi.nlm.nih.gov/pubmed/35741724
http://dx.doi.org/10.3390/genes13060963
work_keys_str_mv AT pfeffergerald multisystemproteinopathyduetovcpmutationsareviewofclinicalheterogeneityandgeneticdiagnosis
AT leegrace multisystemproteinopathyduetovcpmutationsareviewofclinicalheterogeneityandgeneticdiagnosis
AT pontifexcarlys multisystemproteinopathyduetovcpmutationsareviewofclinicalheterogeneityandgeneticdiagnosis
AT fanganiellorobertod multisystemproteinopathyduetovcpmutationsareviewofclinicalheterogeneityandgeneticdiagnosis
AT peckallison multisystemproteinopathyduetovcpmutationsareviewofclinicalheterogeneityandgeneticdiagnosis
AT weihlconradc multisystemproteinopathyduetovcpmutationsareviewofclinicalheterogeneityandgeneticdiagnosis
AT kimonisvirginia multisystemproteinopathyduetovcpmutationsareviewofclinicalheterogeneityandgeneticdiagnosis