胶东地区非综合征型耳聋患者GJB2、SLC26A4、GJB3和12S rRNA基因的突变分析

摘要

目的 调查胶东地区非综合征型耳聋患者4种常见致病基因(GJB2、SLC26A4、GJB3和12S rRNA)的突变特征.方法 采集2015年1月至2017年9月威海市妇幼保健院门诊的420例耳聋患者的外周血,应用基因芯片对患者GJB2基因c.235delC、c.299-300delAT、c.35delG和c.176del16位点,GJB3基因c.538C＞T位点,SLC26A4基因c.2168A＞G和c.IVS7-2A＞G位点,线粒体12S rRNA基因c.1555A＞C和c.1494C＞T位点进行检测,对杂合突变耳聋患者进行基因全编码区测序.结果 共发现GJB2基因突变者84例(20.00％,84/420),其中c.235delC(16.43％)和c.299-300delAT(7.86％)是主要突变位点.SLC26A4基因突变者75例(17.86％,75/420),主要突变位点为c.IVS7-2A＞ G(15.71％),有5.95％患者是由线粒体12S rRNA突变引起,并有1例患者致病基因与GJB3c.538C＞T位点相关.结论 胶东地区非综合征型耳聋疾病患者主要致病基因位点为GJB2 c.235delC和SLC26A4 c.IVS7-2A＞G.此外,线粒体12S rRNA c.1555A＞C突变者的比例较中国其他地区高.%Objective To explore the characteristics of mutations of four common pathogenic genes (GJB2,SLC26A4,GJB3 and 12S rRNA)among patients with nonsyndromic hearing loss (NSHL) from eastern Shandong.Methods Peripheral blood samples of 420 NSHL patients were collected,and a hereditary-deafness-gene microarray was used to detect GJB2 c.235delC,c.299-300delAT,c.35delG and c.176del16 mutations,GJB3 c.538C＞T mutation,SLC26A4 c.2168A＞G and c.IVS7-2A＞G mutations,and 12S rRNA c.1555A ＞ C and c.1494C ＞ T mutations.For patients carrying single heterozygous mutations,the coding regions of the above genes were analyzed with Sanger sequencing.Results The results of the microarray assay and Sanger sequencing showed that 84 patients (20.00％) carried GJB2 mutations,with c.235delC (16.43％) and c.299-300delAT (7.86％) being most common.Seventy-five patients (17.86％) carried SLC26A4 mutations,for which c.IVS7-2A ＞ G accounted for 15.71％.In addition,5.95％ of patients carried 12S rRNA mutations.Only one patient was found to carried GJB3 mutation (c.538C＞T).Conclusion Common pathogenic mutations for NSHL in eastern Shandong included GJB2 c.235delC and SLC26A4 c.IVS7-2A＞G.Of note,5.95％ of patients were due to 12S rRNA m.1555A＞G mutation,which gave a frequency greater than other regions of China.