Screening of SOD1, FUS and TARDBP genes in patients with amyotrophic lateral sclerosis in central-southern China.
Screening of SOD1, FUS and TARDBP genes in patients with amyotrophic lateral sclerosis in central-southern China.
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中国中南地区肌萎缩侧索硬化症患者SOD1、FUS和TARDBP基因筛查
DOI：
10.1038/srep32478
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发表时间：
2016-09-08
影响因子：
4.6
通讯作者：
Shen L
中科院分区：
文献类型：
--
作者：
Hou L;Jiao B;Xiao T;Zhou L;Zhou Z;Du J;Yan X;Wang J;Tang B;Shen L
肌萎缩侧索硬化症（ALS）是一种影响大脑、脑干和脊髓运动神经元的致命性神经退行性疾病。迄今为止，超过30个基因的突变与ALS的发病机制有关。其中，SOD 1、FUS和TARDBP被列为与ALS相关的三个最常见的基因。然而，在中国中南部地区尚未报道突变分析。在这项研究中，我们对中国中南部173例ALS患者（15例家族性ALS和158例散发性ALS）的SOD 1、FUS和TARDBP进行测序，以检测突变。结果，在3例家族性先证者和3例散发性病例中发现了5个SOD 1错义突变，即p.D101N、p.D101G、p.C111Y、p.N86S和p.V87A;在2例家族性先证者中发现了2个FUS突变，包括1个插入突变P525_Y526insY）和错义突变（p.R521H）;在患者中未观察到TARDBP变体。因此，SOD 1突变存在于20.0%的家族性ALS患者和1.9%的散发性ALS患者中，而FUS突变导致13.3%的家族性ALS病例，而TARDBP突变在家族性或散发性ALS病例中罕见。本研究拓宽了ALS患者的已知突变谱，进一步证明了在中国中南部ALS患者中进行基因筛查的必要性。
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting motor neurons of the brain, brainstem and spinal cord. To date, mutations in more than 30 genes have been linked to the pathogenesis of ALS. Among them, SOD1, FUS and TARDBP are ranked as the three most common genes associated with ALS. However, no mutation analysis has been reported in central-southern China. In this study, we sequenced SOD1, FUS and TARDBP in a central-southern Chinese cohort of 173 patients with ALS (15 familial ALS and 158 sporadic ALS) to detect mutations. As a result, five missense mutations in SOD1, namely, p.D101N, p.D101G, p.C111Y, p.N86S and p.V87A, were identified in three unrelated familial probands and three sporadic cases; two mutations in FUS were found in two unrelated familial probands, including an insertion mutation (p.P525_Y526insY) and a missense mutation (p.R521H); no variants of TARDBP were observed in patients. Therefore, SOD1 mutations were present in 20.0% of familial ALS patients and 1.9% of sporadic ALS patients, while FUS mutations were responsible for 13.3% of familial ALS cases and TARDBP mutations were rare in either familial or sporadic ALS cases. This study broadens the known mutational spectrum in patients with ALS and further demonstrates the necessity for genetic screening in ALS patients from central-southern China.
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影响因子：
4.2
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通讯作者：
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