PDF(Pubmed)
Abstract：
UNASSIGNED: Dystonia is a kind of movement disorder but its pathophysiological mechanisms are still largely unknown. Recent evidence reveals that genetical defects may play important roles in the pathogenesis of dystonia.
UNASSIGNED: -To explore possible causative genes in Chinese dystonia patients, DNA samples from 42 sporadic patients with isolated cervical dystonia were subjected to whole-exome sequencing. Rare deleterious variants associated with dystonia phenotype were screened out and then classified according to the American College of Medical Genetics and Genomics (ACMG) criteria. Phenolyzer was used for analyzing the most probable candidates correlated with dystonia phenotype, and SWISS-MODEL server was for predicting the 3D structures of variant proteins.
UNASSIGNED: Among 42 patients (17 male and 25 female) recruited, a total of 36 potentially deleterious variants of dystonia-associated genes were found in 30 patients (30/42, 71.4 %). Four disease-causing variants including a pathogenic variant in PLA2G6 (c.797G > C) and three likely pathogenic variants in DCTN1 (c.73C > T), SPR (c.1A > C) and TH (c.56C > G) were found in four patients separately. Other 32 variants were classified as uncertain significance in 26 patients. Phenolyzer prioritized genes TH, PLA2G6 and DCTN1 as the most probable candidates correlated with dystonia phenotype. Although 3D prediction of DCTN1 and PLA2G6 variant proteins detected no obvious structural alterations, the mutation in DCTN1 (c.73C > T:p.Arg25Trp) was closely adjacent to its key functional domain.
UNASSIGNED: Our whole-exome sequencing results identified a novel variant in DCTN1 in sporadic Chinese patients with isolated cervical dystonia, which however, needs our further study on its exact role in dystonia pathogenesis.
UNASSIGNED: -To explore possible causative genes in Chinese dystonia patients, DNA samples from 42 sporadic patients with isolated cervical dystonia were subjected to whole-exome sequencing. Rare deleterious variants associated with dystonia phenotype were screened out and then classified according to the American College of Medical Genetics and Genomics (ACMG) criteria. Phenolyzer was used for analyzing the most probable candidates correlated with dystonia phenotype, and SWISS-MODEL server was for predicting the 3D structures of variant proteins.
UNASSIGNED: Among 42 patients (17 male and 25 female) recruited, a total of 36 potentially deleterious variants of dystonia-associated genes were found in 30 patients (30/42, 71.4 %). Four disease-causing variants including a pathogenic variant in PLA2G6 (c.797G > C) and three likely pathogenic variants in DCTN1 (c.73C > T), SPR (c.1A > C) and TH (c.56C > G) were found in four patients separately. Other 32 variants were classified as uncertain significance in 26 patients. Phenolyzer prioritized genes TH, PLA2G6 and DCTN1 as the most probable candidates correlated with dystonia phenotype. Although 3D prediction of DCTN1 and PLA2G6 variant proteins detected no obvious structural alterations, the mutation in DCTN1 (c.73C > T:p.Arg25Trp) was closely adjacent to its key functional domain.
UNASSIGNED: Our whole-exome sequencing results identified a novel variant in DCTN1 in sporadic Chinese patients with isolated cervical dystonia, which however, needs our further study on its exact role in dystonia pathogenesis.
摘要：
■肌张力障碍是一种运动障碍，但其病理生理机制尚不清楚。最近的证据表明，遗传缺陷可能在肌张力障碍的发病机理中起重要作用。
■-探讨中国肌张力障碍患者可能的致病基因，对42例散发性宫颈肌张力障碍患者的DNA样品进行了全外显子组测序。筛选出与肌张力障碍表型相关的罕见有害变体，然后根据美国医学遗传学和基因组学学院（ACMG）标准进行分类。Phenolyzer用于分析与肌张力障碍表型相关的最可能候选者，SWISS-MODEL服务器用于预测变异蛋白的3D结构。
■在招募的42名患者（17名男性和25名女性）中，在30例患者(30/42,71.4%)中发现了36种肌张力障碍相关基因的潜在有害变异.四种致病变异，包括PLA2G6中的致病性变异（c.797G>C）和DCTN1中的三种可能的致病性变异（c.73C>T），分别在4例患者中发现了SPR（c.1A>C）和TH（c.56C>G）。在26例患者中，其他32种变体被归类为不确定的意义。酚醛优先基因TH，PLA2G6和DCTN1作为最可能的候选者与肌张力障碍表型相关。虽然DCTN1和PLA2G6变异蛋白的3D预测没有检测到明显的结构改变,DCTN1中的突变（c.73C>T：p。Arg25Trp）与其关键功能域紧密相邻。
■我们的全外显子组测序结果在中国散发性宫颈肌张力障碍患者中发现了DCTN1的一种新变异，然而，其在肌张力障碍发病机制中的确切作用有待进一步研究。
■-探讨中国肌张力障碍患者可能的致病基因，对42例散发性宫颈肌张力障碍患者的DNA样品进行了全外显子组测序。筛选出与肌张力障碍表型相关的罕见有害变体，然后根据美国医学遗传学和基因组学学院（ACMG）标准进行分类。Phenolyzer用于分析与肌张力障碍表型相关的最可能候选者，SWISS-MODEL服务器用于预测变异蛋白的3D结构。
■在招募的42名患者（17名男性和25名女性）中，在30例患者(30/42,71.4%)中发现了36种肌张力障碍相关基因的潜在有害变异.四种致病变异，包括PLA2G6中的致病性变异（c.797G>C）和DCTN1中的三种可能的致病性变异（c.73C>T），分别在4例患者中发现了SPR（c.1A>C）和TH（c.56C>G）。在26例患者中，其他32种变体被归类为不确定的意义。酚醛优先基因TH，PLA2G6和DCTN1作为最可能的候选者与肌张力障碍表型相关。虽然DCTN1和PLA2G6变异蛋白的3D预测没有检测到明显的结构改变,DCTN1中的突变（c.73C>T：p。Arg25Trp）与其关键功能域紧密相邻。
■我们的全外显子组测序结果在中国散发性宫颈肌张力障碍患者中发现了DCTN1的一种新变异，然而，其在肌张力障碍发病机制中的确切作用有待进一步研究。
