Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, China.
Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
J Neurol Neurosurg Psychiatry. 2017 Jul;88(7):540-549. doi: 10.1136/jnnp-2016-315018. Epub 2017 Jan 5.
Genetic studies have shown that , , and are the most common mutated genes in amyotrophic lateral sclerosis (ALS). Here, we performed a meta-analysis to determine the mutation frequencies of these major ALS-related genes in patients with ALS.
We performed an extensive literature research to identify all original articles reporting frequencies of , , and mutations in ALS. The mutation frequency and effect size of each study were combined. Possible sources of heterogeneity across studies were determined by meta-regression, sensitivity analysis and subgroup analysis.
111 studies were included in the meta-analysis. The overall pooled mutation frequencies of these major ALS-related genes were 47.7% in familial amyotrophic lateral sclerosis (FALS) and 5.2% in sporadic ALS (SALS). A significant difference was identified regarding the frequencies of mutations in major ALS genes between European and Asian patients. In European populations, the most common mutations were the repeat expansions (FALS 33.7%, SALS 5.1%), followed by (FALS 14.8%, SALS 1.2%), (FALS 4.2%, SALS 0.8%) and mutations (FALS 2.8%, SALS 0.3%), while in Asian populations the most common mutations were mutations (FALS 30.0%, SALS 1.5%), followed by (FALS 6.4%, SALS 0.9%), (FALS 2.3%, SALS 0.3%) and (FALS 1.5%, SALS 0.2%) mutations.
These findings demonstrated that the genetic architecture of ALS in Asian populations is distinct from that in European populations, which need to be given appropriate consideration when performing genetic testing of patients with ALS.
遗传研究表明，在肌萎缩侧索硬化症（ALS）中，、、和是最常见的突变基因。在这里，我们进行了一项荟萃分析，以确定这些主要的 ALS 相关基因在 ALS 患者中的突变频率。
我们进行了广泛的文献研究，以确定所有报告 ALS 中、、和突变频率的原始文章。合并了每个研究的突变频率和效应大小。通过荟萃回归、敏感性分析和亚组分析确定了研究之间异质性的可能来源。
共有 111 项研究纳入荟萃分析。这些主要 ALS 相关基因在家族性肌萎缩侧索硬化症（FALS）中的总突变频率为 47.7%，在散发性肌萎缩侧索硬化症（SALS）中为 5.2%。在欧洲和亚洲患者中，主要 ALS 基因的突变频率存在显著差异。在欧洲人群中，最常见的突变是重复扩展（FALS 33.7%，SALS 5.1%），其次是（FALS 14.8%，SALS 1.2%）、（FALS 4.2%，SALS 0.8%）和（FALS 2.8%，SALS 0.3%）突变，而在亚洲人群中，最常见的突变是（FALS 30.0%，SALS 1.5%），其次是（FALS 6.4%，SALS 0.9%）、（FALS 2.3%，SALS 0.3%）和（FALS 1.5%，SALS 0.2%）突变。
这些发现表明，亚洲人群中 ALS 的遗传结构与欧洲人群不同，在对 ALS 患者进行基因检测时需要给予适当考虑。
