A novel SOD1 mutation p.V31A identified with a slowly progressive form of amyotrophic lateral sclerosis
A novel SOD1 mutation p.V31A identified with a slowly progressive form of amyotrophic lateral sclerosis
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DOI：
10.1016/j.neurobiolaging.2013.07.012
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发表时间：
2014-01-01
影响因子：
4.2
通讯作者：
Vourc'h, Patrick
中科院分区：
文献类型：
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作者：
Dangoumau, Audrey;Verschueren, Annie;Vourc'h, Patrick
在大约15%的家族性肌萎缩侧索硬化症(ALS)和3%的散发性ALS中，编码超氧化物歧化酶1(SOD1)蛋白的SOD1基因发生了突变。我们在一名49岁的男性患者中发现了一种新的SOD1突变，他在49岁时表现为下肢僵硬，53岁时表现为痉挛性失语，伴有下肢远端肌肉萎缩和股四头肌束束。确诊为肌萎缩侧索硬化。发病11年后，他的病情继续逐渐恶化。在外显子2观察到的杂合性突变导致SOD1蛋白β桶结构域第31位的缬氨酸替换为丙氨酸。在NSC34细胞中的功能分析表明，SOD1(V31A)突变形式的过表达诱导了聚集，降低了细胞存活率。这种突变位于携带大多数ALS相关突变的区域(即催化中心、二聚化区域和β-Barrel的β-链之间的环)之外。总之，我们在一名疾病进展缓慢的患者中发现了一种新的SOD1突变，并支持不同的SOD1突变可以导致不同的ALS表型的观点。(C)2014 Elsevier Inc.保留所有权利。
The SOD1 gene encoding the superoxide dismutase 1 (SOD1) protein is mutated in approximately 15% of familial amyotrophic lateral sclerosis (ALS) and 3% of sporadic ALS. We identified a novel mutation in SOD1 in a man who presented at age 49 with lower limb stiffness, and at age 53, a spastic paraparesia with distal muscular atrophy in the lower limbs and fasciculations in the quadriceps. A diagnosis of ALS was established. Eleven years after disease onset his condition continues gradually and slowly to deteriorate. The heterozygous mutation observed in exon 2 resulted in a valine to alanine substitution at position 31 in the beta-barrel domain of the SOD1 protein. Functional analysis in NSC34 cells showed that the overexpression of the mutant form of SOD1(V31A) induced aggregates and decreased cell viability. This mutation is located outside of the regions carrying most of the ALS-related mutations (i.e., the catalytic center, the region of dimerization, and the loops between the beta-strands of the beta-barrel). In conclusion, we identified a novel SOD1 mutation in a patient with slow disease progression and supported the idea that different SOD1 mutations can lead to distinct ALS phenotypes. (c) 2014 Elsevier Inc. All rights reserved.