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目的:对1例肌萎缩侧索硬化症(amyotrophic lateral sclerosis, ALS)患者进行致病基因变异分析，明确其可能的致病原因。方法:收集患者的外周血标本，应用二代测序技术对患者进行变异筛查，得到候选基因变异位点后，利用Sanger测序技术对该患者及其双亲进行变异位点验证，并在人群中筛查该变异。结果:患者n SOD1基因存在c.420C>G(p.Asn140Lys)杂合变异，其父母均未携带该变异，提示其为新发变异(n de novo)，且既往未见报道。在100名正常对照中未检测到该变异，在HGMD，dbSNP等数据库中未见收录。根据美国医学遗传学与基因组学学会遗传变异分类标准与指南，n SOD1基因c.420C>G (p.Asn140Lys)可判定为致病性变异(PS1+PS2+PM2+PP3)。n 结论:SOD1基因c.420C>G变异可能是该患者的致病原因，新变异的检出丰富了n SOD1基因的变异谱。n “,”Objective:To explore the genetic basis for a Chinese patient with amyotrophic lateral sclerosis (ALS) .Methods:Peripheral blood samples were collected from the patient and his parents for the extraction of genomic DNA. Genetic variant was identified by whole exome sequencing. Candidate variant was verified by Sanger sequencing of his parents and healthy controls.Results:The patient was found to harbor a heterozygous c. 420C>G (p.Asn140Lys) variant of then SOD1 gene. The same variant was not detected in his parents and 100 healthy controls. The variant has not been included in HGMD, dbSNP and other databases.n Conclusion:The c. 420C>G variant of then SOD1 gene may underlie the ALS in this patient. Above finding has enriched the spectrum of SOD1 gene variants.n