Wang Zhanjun, Cai Wanshi, Cui Fang, Cai Tao, Chen Zhaohui, Mao Fengbiao, Teng Huajing, Chen Lin, Wang Jiesi, Sun Zhongsheng, Huang Xusheng, Yu Ping
Department of Neurology, Chinese PLA General Hospital, Beijing 100857, China; Beijing Institutes of Life Science Chinese Academy of Sciences, Beijing 100101, China.
Neurobiol Aging. 2014 Mar;35(3):725.e11-5. doi: 10.1016/j.neurobiolaging.2013.08.024. Epub 2013 Oct 1.
Mutations of Cu-Zn superoxide dismutase (SOD1) have rarely been identified in Chinese patients with amyotrophic lateral sclerosis (ALS). We recently initiated a program to screen mutations of SOD1, TARDBP, and C9orf72 genes, the most commonly mutated genes in ALS patients in Western countries, in Chinese ALS patients. In this study, we report a novel missense SOD1 mutation with a substitution of tryptophan for cysteine at the seventh amino acid (p.C7W, traditionally named p.C6W) based on HUGO Gene Nomenclature in a familial ALS pedigree. We also found that the activities of SOD1 were significantly decreased in the C7W patient and the carriers of the family, compared with the SOD1 activities of normal family members. Compared with reported C7G and C7S patients, analysis of phenotype revealed relatively mild disease phenotypes in C7W patients, which is correlated with less deteriorated alteration in protein structure. Like those of many other familial ALS families, variable clinical phenotypes in the C7W intrafamily suggest that potential genetic modifiers may contribute to this disease.
在中国肌萎缩侧索硬化症（ALS）患者中，很少发现铜锌超氧化物歧化酶（SOD1）的突变。我们最近启动了一个项目，对中国ALS患者的SOD1、TARDBP和C9orf72基因进行突变筛查，这些基因是西方国家ALS患者中最常见的突变基因。在本研究中，我们报告了一个新的SOD1错义突变，在一个家族性ALS家系中，基于HUGO基因命名法，第7个氨基酸处的半胱氨酸被色氨酸取代（p.C7W，传统上称为p.C6W）。我们还发现，与正常家庭成员的SOD1活性相比，C7W患者及其家族携带者的SOD1活性显著降低。与报道的C7G和C7S患者相比，对表型的分析显示C7W患者的疾病表型相对较轻，这与蛋白质结构中较少的恶化改变相关。与许多其他家族性ALS家族一样，C7W家族内的临床表型各异，提示潜在的基因修饰因子可能与该疾病有关。
