摘要：

目的 回顾分析1例SOD1^A4V 基因突变致家族性肌萎缩侧索硬化症患者的临床表型及基因突变特点。方法与结果 男性患者，34 岁。临床表现为四肢下运动神经元损害，呼吸衰竭，双侧腓肠肌肥大；MRI 可见双侧腓肠肌明显水肿；腓肠肌组织活检提示神经源性损害。第二代测序技术显示存在SOD1 基因 c.14C > T（p.Ala5Val）杂合突变，明确诊断为家族性肌萎缩侧索硬化症，该家系证实为家族性肌萎缩侧索硬化症家系。随访至发病 14 个月后死亡。结论 SOD1^A4V 基因突变致家族性肌萎缩侧索硬化症国内罕见，应尽可能同时进行患者及其直系亲属的基因检测，有助于明确诊断及其他家族成员早期诊断。

关键词: 肌萎缩侧索硬化, 肌, 骨骼, 超氧化物歧化酶1, 基因, 突变, 系谱

Abstract:

Objective  To retrospectively analyze the clinical phenotype and gene mutation of one case of familial amyotrophic lateral sclerosis (fALS) caused by SOD1^A4V. Methods and Results The patient was 34-year-old male, presenting with lower motor neuron damage of limbs, dyspnea and bilateral gastrocnemius hypertrophy. MRI indicated obvious edema of bilateral gastrocnemius muscles, and gastrocnemius muscle pathology indicated neurogenic damage. Next-generation sequencing showed the patient had a heterozygous mutation of c.14C > T (p.Ala5Val) of SOD1 gene. The patient was diagnosed as fALS, and the family was diagnosed as fALS pedigree. The patient died 14 months after onset. Conclusions Familial amyotrophic lateral sclerosis caused by SOD1^A4V gene mutation is rarely reported in China. This disease occurs in youth and progresses rapidly. It is necessary to simultaneously detect the gene mutation of patients and their immediate relatives, which is helpful for early and definite diagnosis of other family members.

Key words: Amyotrophic lateral sclerosis, Muscle, skeletal, Superoxide dismutase-1, Genes, Mutation, Pedigree