Genotype-phenotype study in patients with valosin-containing protein mutations associated with multisystem proteinopathy.
Genotype-phenotype study in patients with valosin-containing protein mutations associated with multisystem proteinopathy.
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DOI：
10.1111/cge.13095
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发表时间：
2018-01
影响因子：
3.5
通讯作者：
Kimonis V
中科院分区：
文献类型：
--
作者：
Al-Obeidi E;Al-Tahan S;Surampalli A;Goyal N;Wang AK;Hermann A;Omizo M;Smith C;Mozaffar T;Kimonis V
Valosin-Holding Protein(VCP)是一种参与蛋白质降解和自噬的ATPase，它的突变会导致VCP病，这是一种进行性常染色体显性遗传性成人多系统蛋白病。这项研究的目的是检查这种疾病的表型差异是否可以通过特定的基因突变来解释。因此，我们研究了来自36个家庭的231名个体(118名男性，113名女性)，携带15种不同的VCP突变。我们分析了不同突变与肌病的患病率、发病年龄和严重程度、PDB和FTD以及其他合并症之间的相关性。肌病、PDB和FTD的发生率分别为90%、42%和30%，平均年龄分别为43岁、41岁和56岁。大约9%的VCP突变患者有ALS表型，4%被诊断为帕金森病(PD)，2%被诊断为阿尔茨海默病(AD)。巨大的家庭间和家庭内差异使建立相关性变得困难。我们没有发现突变类型与与VCP病相关的任何临床特征的发生率之间的相关性，除了我们的队列中没有带有R159C突变的PDB，以及与其他分子亚型相比，R159C具有较晚的肌病发病年龄。含有Valosin的蛋白(VCP)的突变会导致包涵体肌病、骨佩吉特病、额颞叶痴呆、嗜肌性侧索硬化症和帕金森氏病。我们研究了来自36个家系的最大个体群体(总计231：118名男性，113名女性)，携带15种不同的VCP突变，以建立基因-表型相关性。较大的家族内和家族间差异使得除了R159C突变的较晚发病年龄外，很难建立相关性。
Mutations in valosin-containing protein (VCP), an ATPase involved in protein degradation and autophagy, cause VCP disease, a progressive autosomal dominant adult onset multisystem proteinopathy. The goal of this study is to examine if phenotypic differences in this disorder could be explained by the specific gene mutations. We therefore studied 231 individuals (118 males, 113 females) from 36 families carrying 15 different VCP mutations. We analyzed correlation between the different mutations and prevalence, age of onset and severity of myopathy, PDB, and FTD, and other comorbidities. Myopathy, PDB and FTD was present in 90%, 42% and 30% of the patients respectively, beginning at an average age of 43 years, 41 years, and 56 years respectively. Approximately 9% of patients with VCP mutations had an ALS phenotype, 4% had been diagnosed with Parkinson’s disease (PD), and 2% had been diagnosed with Alzheimer’s disease (AD). Large inter and intra-familial variation made establishing correlations difficult. We did not find a correlation between the mutation type and the incidence of any of the clinical features associated with VCP disease, except for the absence of PDB with the R159C mutation in our cohort and R159C having a later age of onset of myopathy compared to other molecular subtypes. Mutations in valosin-containing protein (VCP) cause inclusion body myopathy, Paget disease of bone, frontotemporal dementia, amyotropic lateral sclerosis and Parkinson’s disease. We studied the largest group of individuals (total 231: 118 males, 113 females) from 36 families carrying 15 different VCP mutations to establish genotype-phenotype correlation. Large intra-familial and interfamilial variations made establishing correlations difficult to establish except for later age of onset with R159C mutations.
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影响因子：
4
作者：
Kenna KP;McLaughlin RL;Byrne S;Elamin M;Heverin M;Kenny EM;Cormican P;Morris DW;Donaghy CG;Bradley DG;Hardiman O
通讯作者：
Hardiman O
影响因子：
--
作者：
Jerath NU;Crockett CD;Moore SA;Shy ME;Weihl CC;Chou TF;Grider T;Gonzalez MA;Zuchner S;Swenson A
通讯作者：
Swenson A
影响因子：
9.9
作者：
Haubenberger, D;Bittner, RE;Zimprich, A
通讯作者：
Zimprich, A
影响因子：
4.2
作者：
Bersano, Anna;Del Bo, Roberto;Corti, Stefania
通讯作者：
Corti, Stefania
影响因子：
6
作者：
Cairns, Nigel J.;Neumann, Manuela;Mackenzie, Ian R. A.
通讯作者：
Mackenzie, Ian R. A.