Wen Xinmei, Zhu Wenjia, Xia Nan L, Li Qianwen, Di Li, Zhang Shu, Chen Hai, Lu Yan, Wang Min, Xu Min, Wang Suobin, Shen Xin-Ming, Lu Jie, Da Yuwei
Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.
Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Front Genet. 2021 Nov 17;12:776831. doi: 10.3389/fgene.2021.776831. eCollection 2021.
Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease, characterized by a great variety of both clinical presentations and genetic causes. Previous studies had identified two different missense mutations in (p.R116C and p.R116G) causing familial ALS. In this study, we report a novel heterozygous missense mutation in the gene (p.R116S) in a family with inherited ALS manifested as fast-deteriorating pure lower motor neuron symptoms. The patient displayed similar clinical picture and prognostic value to previous reported cases with different R116 substitution mutations. Modeling of all R116 substitutions in the resolved SOD1 protein structure revealed a shared mechanism with destroyed hydrogen bonds between R116 and other two residues, which might lead to protein unfolding and oligomer formation, ultimately conferring neurotoxicity.
肌萎缩侧索硬化症（ALS）是运动神经元疾病最常见的形式，其临床表现和遗传病因多种多样。先前的研究已在（p.R116C和p.R116G）中鉴定出两种不同的错义突变，可导致家族性ALS。在本研究中，我们报告了一个患有遗传性ALS的家系中，基因（p.R116S）出现了一种新的杂合错义突变，该家系表现为快速恶化的纯下运动神经元症状。该患者表现出与先前报道的具有不同R116替代突变的病例相似的临床症状和预后价值。在解析的SOD1蛋白质结构中对所有R116替代进行建模，揭示了一种共同机制，即R116与其他两个残基之间的氢键被破坏，这可能导致蛋白质解折叠和寡聚体形成，最终产生神经毒性。
