Recent studies have identified SOD1, FUS, TARDBP and C9orf72 as major ALS-related genes in both European and Asian populations. However, significant differences exist in the mutation frequencies of these genes between various ancestral backgrounds. This study aims to identify the frequency of mutations in the common causative ALS genes in a multi-ethnic Malaysian cohort. We screened 101 Malaysian ALS patients including 3 familial and 98 sporadic cases for mutations in the coding regions of SOD1, FUS, and TARDBP by Sanger sequencing. The C9orf72 hexanucleotide repeat expansion was screened using the repeat-primed polymerase chain reaction assay. Mutations were found in 5.9% (6/101) of patients including 3.0% (3/101) of patients with the previously reported SOD1 missense mutations (p.V48A and p.N87S) and 3.0% (3/101) of patients with the C9orf72 repeat expansion. No mutations were found in the FUS and TARDBP genes. This study is the first to report the mutation frequency in an ethnically diverse Malaysian ALS population and warrants further investigation to reveal novel genes and disease pathways.

最近的研究已将SOD1、FUS、TARDBP和C9orf72 确定为欧洲和亚洲人群中主要的 ALS 相关基因。然而，不同祖先背景之间这些基因的突变频率存在显着差异。本研究旨在确定马来西亚多民族队列中常见致病 ALS 基因的突变频率。我们通过 Sanger 测序筛选了 101 名马来西亚 ALS 患者，其中包括 3 名家族性和 98 名散发病例，以确定SOD1、FUS和TARDBP编码区的突变。C9orf72 _使用重复引发聚合酶链反应测定筛选六核苷酸重复扩增。在 5.9% (6/101) 的患者中发现了突变，包括 3.0% (3/101) 的具有先前报道的SOD1错义突变（p.V48A 和 p.N87S）的患者和 3.0% (3/101) 的患者C9orf72重复扩展。在FUS和TARDBP基因中未发现突变。这项研究是第一个报告种族多样化的马来西亚 ALS 人群中的突变频率，并需要进一步调查以揭示新的基因和疾病途径。