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
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DOI：
10.1016/j.jns.2016.07.048
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发表时间：
2016-09-15
影响因子：
4.4
通讯作者：
Pedroso, Jose Luiz
中科院分区：
文献类型：
--
作者：
Abrahao, Agessandro;Neto, Osorio Abath;Pedroso, Jose Luiz
背景资料：VCP（含缬沙汀蛋白基因）变体与外周和中枢神经退行性过程相关，包括包涵体肌病（IBM）、佩吉特骨病（PDB）、额颞叶痴呆（FTD）和家族性肌萎缩侧索硬化（ALS）14型。IBM、PDB（IBMPFD 1）的组合可以在一个个体中呈现。然而，IBMPFD 1与ALS在同一家族中的关联很少见。方法：我们报告了来自巴西亲属的三名具有家族内表型变异的个体。对先证者进行全外显子组测序（WES），发现了一种新的VCP变异体。对先证者及其家属进行VCP桑格测序，以证实WES发现和分离。我们进行了一个系统的文献综述的基因型表型VCP correlations.Results：每个人都提出了肌病与镶边空泡，ALS，或FTD。没有PDB。先证者的WES在VCP外显子3中鉴定出杂合变体c.271A> T（p.Asn91Tyr）。桑格测序证实了这种变体的分离在常染色体显性pattern.Conclusion：本研究扩大了VCP基因的错义突变的基因型谱与一种新的p.Asn9lTyr的变体中发现的巴西家庭提出了不寻常的intrafamiliar协会肌病与镶边空泡，ALS和FTD。(C)2016爱思唯尔B.V.保留所有权利。
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.