Soong Bing-Wen, Lin Kon-Ping, Guo Yuh-Cherng, Lin Chou-Ching K, Tsai Pei-Chien, Liao Yi-Chu, Lu Yi-Chun, Wang Shuu-Jiun, Tsai Ching-Piao, Lee Yi-Chung
Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan; Brain Research Center, National Yang-Ming University, Taipei, Taiwan.
Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan.
Neurobiol Aging. 2014 Oct;35(10):2423.e1-6. doi: 10.1016/j.neurobiolaging.2014.05.008. Epub 2014 May 11.
Identification of genetic mutations has been of burgeoning importance in amyotrophic lateral sclerosis (ALS) in recent years. The aim of this study was to determine the frequency and spectrum of mutations in major ALS-causing genes in a Taiwanese ALS cohort of Han Chinese origin. Mutational analyses of the SOD1, TARDBP, FUS, OPTN, VCP, UBQLN2, SQSTM1, PFN1, HNRNPA1, and HNRNPA2B1 genes were carried out by direct sequencing in 161 unrelated patients with ALS, including 30 with familial ALS (FALS) and 131 with sporadic ALS (SALS). The CAG repeat size in ATXN2 and the GGGGCC repeat expansion in C9ORF72 of the patients were also investigated. Mutations were identified in 33 patients (20.5%, 33/161), including 22 with FALS and 11 with SALS. Mutations were identified most frequently in SOD1 (7.5%). Three mutations are novel, including SOD1 p.G10A, SOD1 p.D83N, and OPTN p.L494W. These findings broaden the spectrum of ALS-causing mutations and are indispensable for designing optimal strategies of mutational analysis and genetic counseling of ALS for patients of Chinese origin.
近年来，基因突变的鉴定在肌萎缩侧索硬化症（ALS）中变得越来越重要。本研究的目的是确定源自中国台湾汉族ALS队列中主要致病基因的突变频率和谱。通过直接测序对161例无亲缘关系的ALS患者进行SOD1、TARDBP、FUS、OPTN、VCP、UBQLN2、SQSTM1、PFN1、HNRNPA1和HNRNPA2B1基因的突变分析，其中包括30例家族性ALS（FALS）患者和131例散发性ALS（SALS）患者。还研究了患者中ATXN2的CAG重复序列长度和C9ORF72的GGGGCC重复序列扩增情况。在33例患者（20.5%，33/161）中鉴定出突变，其中包括22例FALS患者和11例SALS患者。SOD1基因的突变最为常见（7.5%）。三个突变是新发现的，包括SOD1 p.G10A、SOD1 p.D83N和OPTN p.L494W。这些发现拓宽了ALS致病突变的谱，对于为华裔患者设计ALS突变分析和遗传咨询的最佳策略不可或缺。
