Wu Chujun, Fan Dongsheng
Department of Neurology, Peking University Third Hospital Beijing, China.
Front Aging Neurosci. 2016 Dec 6;8:291. doi: 10.3389/fnagi.2016.00291. eCollection 2016.
Juvenile amyotrophic lateral sclerosis (jALS) is a rare form of ALS with an onset age of less than 25 years and is frequently thought to be genetic in origin. gene mutations have been reported to be associated with the SPG28 subtype of autosomal recessive HSP but have never been reported in jALS patients. Gene screens for the causative genes of ALS, HSP and CMT using next-generation sequencing (NGS) technologies were performed on a jALS patient. Sanger sequencing was used to validate identified variants and perform segregation analysis. We identified a novel c.1483A>G (p.Met495Val) homozygous missense mutation of the gene in the jALS patient. All of his parents and young bother were heterozygous for this mutation. The mutation was not found in 800 Chinese control subjects or the database of dbSNP, ExAC and 1000G. The novel c.1483A>G (p.Met495Val) missense mutation of the gene could be a causative mutation of autosomal recessive jALS.
青少年肌萎缩侧索硬化症（jALS）是肌萎缩侧索硬化症的一种罕见形式，发病年龄小于25岁，通常被认为起源于遗传。据报道，基因突变与常染色体隐性遗传性痉挛性截瘫（HSP）的SPG28亚型相关，但从未在jALS患者中报道过。我们对一名jALS患者使用新一代测序（NGS）技术进行了肌萎缩侧索硬化症、遗传性痉挛性截瘫和遗传性运动感觉神经病致病基因的基因筛查。采用桑格测序法验证已鉴定的变异并进行分离分析。我们在该jALS患者中鉴定出该基因的一种新的纯合错义突变c.1483A>G（p.Met495Val）。他的父母和弟弟均为该突变的杂合子。在800名中国对照受试者或dbSNP、ExAC和1000G数据库中未发现该突变。该基因新的c.1483A>G（p.Met495Val）错义突变可能是常染色体隐性jALS的致病突变。
