Wu Rui, Chen Wen-Tian, Dou Wei-Kang, Zhou Hui-Min, Shi Ming
Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China.
Department of Neurology, Xi'an People's Hospital (Xi'an Fourth Hospital), Xi'an, 710004, Shaanxi Province, China.
Heliyon. 2024 May 23;10(11):e31885. doi: 10.1016/j.heliyon.2024.e31885. eCollection 2024 Jun 15.
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.
-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.
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 (c.797G > C) and three likely pathogenic variants in (c.73C > T), (c.1A > C) and (c.56C > G) were found in four patients separately. Other 32 variants were classified as uncertain significance in 26 patients. Phenolyzer prioritized genes , and as the most probable candidates correlated with dystonia phenotype. Although 3D prediction of and variant proteins detected no obvious structural alterations, the mutation in (c.73C > T:p.Arg25Trp) was closely adjacent to its key functional domain.
Our whole-exome sequencing results identified a novel variant in in sporadic Chinese patients with isolated cervical dystonia, which however, needs our further study on its exact role in dystonia pathogenesis.
肌张力障碍是一种运动障碍，但其病理生理机制仍大多未知。最近的证据表明，基因缺陷可能在肌张力障碍的发病机制中起重要作用。
为了探索中国肌张力障碍患者中可能的致病基因，对42例散发性孤立性颈部肌张力障碍患者的DNA样本进行全外显子组测序。筛选出与肌张力障碍表型相关的罕见有害变异，然后根据美国医学遗传学与基因组学学会（ACMG）标准进行分类。使用Phenolyzer分析与肌张力障碍表型最相关的候选基因，使用SWISS-MODEL服务器预测变异蛋白的三维结构。
在招募的42例患者（17例男性和25例女性）中，30例患者（30/42，71.4%）共发现36个与肌张力障碍相关基因的潜在有害变异。在4例患者中分别发现了4个致病变异，包括一个在（c.797G>C）的致病变异和3个在（c.73C>T）、（c.1A>C）和（c.56C>G）的可能致病变异。其他32个变异在26例患者中被分类为意义未明。Phenolyzer将基因、和列为与肌张力障碍表型最相关的候选基因。虽然对和变异蛋白的三维预测未检测到明显的结构改变，但（c.73C>T:p.Arg25Trp）的突变紧邻其关键功能域。
我们的全外显子组测序结果在散发性中国孤立性颈部肌张力障碍患者中鉴定出一个新的变异，但需要进一步研究其在肌张力障碍发病机制中的确切作用。
