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

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.