One family, one gene and three phenotypes: A novel VCP (valosin-containing protein) mutation associated with myopathy with rimmed vacuoles, amyotrophic lateral sclerosis and frontotemporal dementia

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dc.contributor.authorAbrahao, Agessandro [UNIFESP]
dc.contributor.authorNeto, Osorio Abath
dc.contributor.authorKok, Fernando
dc.contributor.authorZanoteli, Edmar
dc.contributor.authorSantos, Bibiana
dc.contributor.authorVieira de Rezende Pinto, Wladimir Bocca [UNIFESP]
dc.contributor.authorPovoas Barsottini, Orlando Graziani [UNIFESP]
dc.contributor.authorBulle Oliveira, Acary Souza [UNIFESP]
dc.contributor.authorPedroso, Jose Luiz [UNIFESP]
dc.date.accessioned2019-07-22T15:46:33Z
dc.date.available2019-07-22T15:46:33Z
dc.date.issued2016
dc.description.abstractBackground: VCP (valosin-containing protein gene) variants have been associated with peripheral and central neurodegenerative processes, including inclusion body myopathy (IBM), Paget disease of bone (PDB), frontotemporal dementia (FTD), and familial amyotrophic lateral sclerosis (ALS) type 14. The combination of IBM, PDB (IBMPFD1) can presented in one individual. However, the association of IBMPFD1 and ALS in the same family is rare. Methods: We reported three individuals from a Brazilian kindred with intrafamilial phenotype variability. Whole exome sequencing (WES) of the proband was performed and revealed a novel VCP variant. VCP Sanger sequencing was performed in the proband and his family members to confirm WES finding and segregation. We performed a systematic review of the literature regarding the genotypic-phenotypic VCP correlations. Results: Each individual presented with either myopathy with rimmed vacuoles, ALS, or FTD. There was no PDB. WES of the proband identified the heterozygous variant c.271A> T (p.Asn91Tyr) in the exon 3 of VCP. Sanger sequencing confirmed the segregation of this variant in an autosomal-dominant pattern. Conclusion: This study expands the genotypic spectrum of the missense mutations of the VCP gene with a novel p.Asn9lTyr variant found in a Brazilian family presenting with the unusual intrafamiliar association of myopathy with rimmed vacuoles, ALS and FTD. (C) 2016 Elsevier B.V. All rights reserved.en
dc.description.affiliationFed Univ Sao Paulo UNIFESP, Dept Neurol & Neurosurg, Div Gen Neurol & Ataxias, Sao Paulo, SP, Brazil
dc.description.affiliationUniv Sao Paulo FMUSP, Dept Neurol, Fac Med, Sao Paulo, Brazil
dc.description.affiliationMendel Genom Anal, Sao Paulo, SP, Brazil
dc.description.affiliationFed Univ Sao Paulo UNIFESP, Dept Neurol & Neurosurg, Div Neuromuscular Dis, Sao Paulo, SP, Brazil
dc.description.affiliationUnifespFed Univ Sao Paulo UNIFESP, Dept Neurol & Neurosurg, Div Gen Neurol & Ataxias, Sao Paulo, SP, Brazil
dc.description.affiliationUnifespFed Univ Sao Paulo UNIFESP, Dept Neurol & Neurosurg, Div Neuromuscular Dis, Sao Paulo, SP, Brazil
dc.description.sourceWeb of Science
dc.format.extent352-358
dc.identifierhttp://dx.doi.org/10.1016/j.jns.2016.07.048
dc.identifier.citationJournal Of The Neurological Sciences. Amsterdam, v. 368, p. 352-358, 2016.
dc.identifier.doi10.1016/j.jns.2016.07.048
dc.identifier.issn0022-510X
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/50966
dc.identifier.wosWOS:000382415700073
dc.language.isoeng
dc.publisherElsevier Science Bv
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectInclusion body myopathyen
dc.subjectFrontotemporal dementiaen
dc.subjectAmyotrophic lateral sclerosisen
dc.subjectVCPen
dc.subjectValosin-containing proteinen
dc.titleOne family, one gene and three phenotypes: A novel VCP (valosin-containing protein) mutation associated with myopathy with rimmed vacuoles, amyotrophic lateral sclerosis and frontotemporal dementiaen
dc.typeinfo:eu-repo/semantics/article
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