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

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

Author Abrahao, Agessandro Autor UNIFESP Google Scholar
Neto, Osorio Abath Google Scholar
Kok, Fernando Google Scholar
Zanoteli, Edmar Google Scholar
Santos, Bibiana Google Scholar
Vieira de Rezende Pinto, Wladimir Bocca Autor UNIFESP Google Scholar
Povoas Barsottini, Orlando Graziani Autor UNIFESP Google Scholar
Bulle Oliveira, Acary Souza Autor UNIFESP Google Scholar
Pedroso, Jose Luiz Autor UNIFESP Google Scholar
Abstract Background: 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.
Keywords Inclusion body myopathy
Frontotemporal dementia
Amyotrophic lateral sclerosis
VCP
Valosin-containing protein
Language English
Date 2016
Published in Journal Of The Neurological Sciences. Amsterdam, v. 368, p. 352-358, 2016.
ISSN 0022-510X (Sherpa/Romeo, impact factor)
Publisher Elsevier Science Bv
Extent 352-358
Origin http://dx.doi.org/10.1016/j.jns.2016.07.048
Access rights Closed access
Type Article
Web of Science ID WOS:000382415700073
URI http://repositorio.unifesp.br/handle/11600/50966

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