Zhang Hang, Cai Wanshi, Chen Siyu, Liang Jialong, Wang Zhanjun, Ren Yuting, Liu Wenxiu, Zhang Xiaolan, Sun Zhongsheng, Huang Xusheng
a Department of Neurology , Chinese PLA General Hospital , Beijing , China.
b Beijing Institutes of Life Science, Chinese Academy of Sciences , Beijing , China.
Amyotroph Lateral Scler Frontotemporal Degener. 2018 Aug;19(5-6):419-425. doi: 10.1080/21678421.2018.1432659. Epub 2018 Feb 7.
We investigated all coding regions of 17 known amyotrophic lateral sclerosis (ALS)-related genes in 311 sporadic ALS patients who were of Chinese ancestry using next-generation sequencing technology. All nonsynonymous variants identified were confirmed by Sanger sequencing. 29 (9.32%) patients harbored at least one pathogenic or likely pathogenic variants. Nine (2.8%) patients harbored two or three variants which frequency <1% in population databases that may be related to oligogenic pathogenesis. A higher allele frequency was observed in East Asian than in European patients for the majority variants identified in this screening, which may indicate that genetic factors are responsible for the different clinical characteristics between Chinese and European ALS patients. Our study reports the results of extensive genetic screening and is the first to investigate the possible oligogenic pathogenesis in Chinese sporadic ALS patients. These findings are useful for exploring ALS pathogenesis and treatment strategies.
我们使用下一代测序技术，对311名具有中国血统的散发性肌萎缩侧索硬化症（ALS）患者中17个已知的与ALS相关基因的所有编码区进行了研究。所有鉴定出的非同义变异均通过桑格测序进行了确认。29名（9.32%）患者携带至少一种致病性或可能致病性变异。9名（2.8%）患者携带两个或三个在人群数据库中频率<1%的变异，这些变异可能与寡基因发病机制有关。在此次筛查中鉴定出的大多数变异，东亚患者的等位基因频率高于欧洲患者，这可能表明遗传因素导致了中国和欧洲ALS患者临床特征的差异。我们的研究报告了广泛基因筛查的结果，并且首次对中国散发性ALS患者中可能的寡基因发病机制进行了研究。这些发现有助于探索ALS的发病机制和治疗策略。
