Journal article
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
Journal of the neurological sciences, Vol.368, pp.352-358
09/15/2016
DOI: 10.1016/j.jns.2016.07.048
PMID: 27538664
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.
Details
- Title: Subtitle
- 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
- Creators
- Agessandro Abrahao - Universidade Federal de São PauloOsorio Abath Neto - Universidade de São PauloFernando Kok - Universidade de São PauloEdmar Zanoteli - Universidade de São PauloBibiana Santos - MendelicsWladimir Bocca Vieira de Rezende Pinto - Federal ReserveOrlando Graziani Povoas Barsottini - Federal ReserveAcary Souza Bulle Oliveira - Federal ReserveJose Luiz Pedroso - Universidade Federal de São Paulo
- Resource Type
- Journal article
- Publication Details
- Journal of the neurological sciences, Vol.368, pp.352-358
- Publisher
- Elsevier
- DOI
- 10.1016/j.jns.2016.07.048
- PMID
- 27538664
- ISSN
- 0022-510X
- eISSN
- 1878-5883
- Number of pages
- 7
- Language
- English
- Date published
- 09/15/2016
- Academic Unit
- Pathology
- Record Identifier
- 9984277459102771
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