贵州省人工耳蜗植入患儿的常见耳聋基因突变位点分析  

Analysis of Mutant Loci of Common Deafness Genes in pediatric Cochlear Implant recipients in Guizhou Province

作　　者：兰莉[1] 叶清[1] 杨可婕[1] 韩巍[1] 张嫄[1] 王敏[1] 黄维[1] 曹祖威[1] 刘宇清[1] 陶方英[1] 杨雪 王幼勤[1] 李斐[1] LAN Li;YE Qing;YANG Kejie;HAN Wei;ZHANG Yuan;WANG Min;HUANG Wie;CAO Zuwei;LIU Yuqing;TAO Fangying;YANG Xue;WANG Youqin;LI Fei(Guizhou Provincial People's Hospital)

机构地区：[1]贵州省人民医院听力中心

出　　处：《中华耳科学杂志》2019年第4期552-557,共6页Chinese Journal of Otology

基　　金：贵州省科技计划项目(合同编号--黔科合LH字【2016】7173)~~

摘　　要：目的分析贵州省85例人工耳蜗植入患儿常见耳聋基因突变特点,初步了解其耳聋基因热点突变谱系及频率。方法采集贵州省85例平均年龄为3.31±1.67岁的人工耳蜗植入患儿的外周血,提取基因组DNA,采用基质辅助激光解吸电离飞行时间质谱技术(MALDI-TOF-MS)进行SNP基因分型检测。对GJB2,SLC26A4,GJB3 and mtDNA12srRNA4个基因(GJB2基因c.35delG、c.167delT、c.176-191del16、c.235delC、c.299-300delAT,GJB3基因c.538C>T、c.547G>A、SLC26A4基因c.281C>T、c.589G>A、C.919-2A>G、c.1174A>T、c.1226G>A、c.1229C>T、IVS15+5G>A、c.1975G>C、c.2027T>A、c.2162C>T、c.2168A>G,线粒体12SrRNA基因1555A>G、1494C>T)的20个位点进行检测。结果85例人工耳蜗植入患儿中,共有25例(29.41%)患儿携带不同的常见致聋基因,1例携带GJB2、SLC26A4双基因突变。其中GJB2基因突变15例(17.65%)(含前述1例双基因突变者),其中纯合突变9例(10.59%),复合杂合突变3例(3.53%),单杂合突变2例(2.35%);SLC26A4基因突变9例(10.59%)(含前述1例双基因突变者),其中纯合突变2例(2.35%),单杂合突变6例(7.06%);DNA12SrRNA基因突变2例(2.35%),m.1555A>G同质突变1例(1.18%),m.1494C>T均质突变1例(1.18%);GJB3检出率为0。汉族与少数民族的突变检出率分别为36.73%、19.44%。结论人工耳蜗植入患儿中很多是遗传因素造成的,贵州省人工耳耳蜗植入患儿以GJB2基因和SLC26A4基因为最主要的致病基因,其中c.235delC突变为最常见突变位点,其次为C.919-2A>G突变。汉族患者基因突变检出率较少数民族患者高。Objective To report characteristics of common deafness gene mutations in 85 children with cochlear implants in Guizhou Province to try to understand the hotspot mutation spectrum and frequency of deafness gene in this particular population.Methods Peripheral blood samples were collected from 85 children using cochlear implants in Guizhou Province.Genomic DNA was extracted.SNP genotyping was performed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF-MS)for 20 mutation sites of four deafness related genes,in-cluding the GJB2,SLC26A4,GJB3 and mtDNA12srRNA genes.Results Among 85 children,25(29.41%)carried com-mon deafness gene mutations and 1 carried GJB2 and SLC26A4 double gene mutations.Among them,GJB2 gene muta-tions were detected in 15 cases(17.65%),including homozygous(n=9,10.59%),compound heterozygous(n=3,3.53%)and single heterozygous mutations(n=2,2.35%),as well as the GJB2 and SLC26A4 double gene mutations mentioned above.SLC26A4 gene mutations involved 9 cases(10.59%)as homozygous(n=2,2.35%)or single heterozygous(n=6,7.06%)mutation,as well as the GJB2 and SLC26A4 double gene mutations mentioned above.DNA12SrRNA gene muta-tion was detected in 2 cases(2.35%).There was 1 case(1.18%)showing m.1555A>G and 1 case(1.18%)showing m.1494C>T homogeneous mutations.No mutation of the GJB3 gene was detected.The mutation detection rates were 36.73%and 19.44%for the ethnic Han and minority groups,respectively.Conclusion Hearing in many of the children needing cochlear implantation is caused by genetic mutations.The GJB2 gene and SL26A4 genes are the dominant pathogenic genes in Guizhou Province.The most common mutation site is c.235delC,followed by C.919-2A>G muta-tion.The rate of gene mutation in Han patients is higher than that in ethnic minority children.

关 键 词：耳聋 基因 突变 人工耳蜗植入 

分 类 号：R764[医药卫生—耳鼻咽喉科]