应用高通量基因捕获技术寻找非综合征型耳聋新的热点突变  

Identification of novel common mutations among patients with non-syndromic hearing loss with high-throughput gene capture technology

作　　者：周永安[1] 曾红艳[2] 栗向韶[3] 杨慧芳[2] 郭伟[2] 郝子琪[3] 李鹏丽[3] 李娇[3] 赵晓丽[2] 王湘[3] 夏丽 麻思琪 

机构地区：[1]山西医科大学第二医院,太原030001 [2]山西医科大学研究生院,太原030001 [3]太原市中心医院,030009 [4]山西省华信瑞安生物科技有限公司,太原030006

出　　处：《中华医学遗传学杂志》2016年第6期758-761,共4页Chinese Journal of Medical Genetics

基　　金：山西省科技攻关项目（20140313018-6）

摘　　要：目的探索常见耳聋致病基因新的热点突变，并评估高通量基因捕获技术在非综合征型耳聋基因诊断中的应用价值。方法应用高通量基因捕获技术对耳聋致病基因GJB2、GJB3、SLC26A4、线粒体12SrRNA的20个常见致病位点未发现突变的18例具有明确家族史的耳聋患者（分别来自不同的家系）进行检测，并采用Sanger法对疑似突变进行验证。结果高通量测序在18例患者中共检测到8个耳聋相关基因的15种突变，其中包括14种错义突变以及1种剪切突变，其中3种错义突变（P．C2184G、P．L2825P、P．H1888Y）既往未见报道。新突变的致病性尚需进一步的验证。P．L445W、P．D866N、IVS919-2A＞G为热点致病突变。结论高通量基因捕获技术准确检测出P．L445W、P．D866N、IVS919-2A＞G为新的致病热点突变，对耳聋诊断及病因筛查具有重要的临床价值。Objective To identify novel common mutations among patients with non-syndromic hearing loss （NSHL）. Methods High-throughput gene capture technology was used to analyze 18 patients with NSHL in whom common mutations of deafness genes including GJB2, SLC26A4, GJB3, and mtDNA were excluded. Suspected mutation was verified with Sanger sequencing. Results Next generation sequencing has identified 62 mutations in 29 genes associated with hearing loss, which included 54 missense mutations, 4 splicing mutations, 3 deletional mutations, and 1 nonsense mutation. Mutations occurring more than twice in the 18 patients were verified by Sanger sequencing. This has confirmed 15 mutations in 8 genes, including 3 missense mutations （p. C2184G, p. L2825P, p. H1888Y） which have not been reported previously. Meanwhile, p. L445W, p. D866N, and IVSglg-2A〉G were common causative mutations. Conclusion A number of common causative mutations, e. g. , p. L445W, p. D866N, IVS919-2A〉G, have been identified by high-throughput capture technology, which may facilitate the research and genetic diagnosis for hearing loss.

关 键 词：耳聋 基因诊断 高通量基因捕获技术 测序 

分 类 号：R4[医药卫生—临床医学] R76