中国人群散发性肌萎缩侧索硬化SETX基因突变筛查  

Screening of the SETX gene in sporadic amyotrophic lateral sclerosis patients of Chinese origin

作　　者：张航 梁加龙 陈思宇[1] 王占军 杨飞[1] 崔芳[1] 任雨婷 刘文秀[1] 孙中生 黄旭升[1] Zhang Hang;Liang Jialong;Chen Siyu;Wang Zhanjun;Yang Fei;Cui Fang;Ren Yuting;Liu Wenxiu;Sun Zhongsheng;Huang Xusheng(Department of Neurology,Chinese PLA General Hospital,Beijing 100853,China Corresponding authors ： Sun Zhongsheng,Institute of Genetics and Developmental Biology,Chinese Academy of Sciences,Beijing 100101,China)

机构地区：[1]解放军总医院神经内科,北京100853 [2]中国科学院遗传与发育生物学研究所,北京100853 [3]海军总医院神经内科,北京100853

出　　处：《中华医学杂志》2018年第33期2628-2631,共4页National Medical Journal of China

基　　金：国家自然科学基金（81671278,81601096）;海南省重点研发计划（ZDYF2016120）;解放军总医院百项优势项目（YS201415）

摘　　要：目的筛查中国人群散发性肌萎缩侧索硬化相关致病基因SETX突变情况。方法自2010年1月至2014年12月在解放军总医院神经内科采集311例散发性肌萎缩侧索硬化患者和311名健康对照者的临床资料和外周静脉血，提取基因组DNA。通过聚合酶链式反应扩增SETX基因编码区并进行测序以筛查基因突变。应用在线软件SIFT与PolyPhen-2预测突变致病性。应用统计软件SPSS22．0对患者临床特点进行分析。结果12例患者携带11种非同义突变（3．86％），其中5（1．61％）例患者携带高致病性突变。携带SETX基因突变的患者在起病年龄上与其他患者无明显差异。结论SETX基因突变可能是中国人群部分散发性肌萎缩侧索硬化患者的病因之一。Objective To investigate all coding regions of amyotrophic lateral sclerosis （ALS）- related gene Senataxin （SETX） in sporadic amyotrophic lateral sclerosis patients of Chinese origin. Methods From January 2010 to December 2014, the peripheral venous blood samples and clinical data were collected from 311 patients with sporadic amyotrophic lateral sclerosis （SALS） and 311 healthy controls who were of Chinese ancestry from the Department of Neurology, Chinese PLA General Hospital. Genomic DNA was extracted from peripheral venous blood of all participants using standard methods. The coding regions of SETX were amplified by polymerase chain reaction （PCR） and screened for mutations using next-generation sequencing technology. The online software SIFT and PolyPhen-2 were used to analyze the conservation of an altered amino acid and predict the potential pathogenicity of identified mutations. The SPSS 22. 0 software was used to analyze the clinical feature of all participants. Results Tenkinds of rare and one novel nonsynonymous mutations were identified and were absent in 311 controls. Twelve （3.86%） patients carried one SETX gene mutation. Five （1.61%） out of above-mentioned 12 patients carried highly pathogenic mutations including p. Pro1868Leu （ c. 5603G 〉 A）, p. Pro1331Leu （ c. 3992G 〉 A）, p. Glu756Val （ e. 2267T 〉 A）, p. Leu564Val （ c. 1690A 〉 C）, and p. Asn144Ser （ c. 431T 〉 C）. Patients carried SETX mutations were not different from other patients in onset age. Conclusion Mutations in SETX are likely to be a pathogenesis for Chinese sporadic amyotrophic lateral sclerosis.

关 键 词：肌萎缩侧索硬化 SETX基因 基因筛查 

分 类 号：R440[医药卫生—诊断学] R744.8[医药卫生—临床医学]