非综合征型耳聋患者耳聋易感基因突变的检测分析

Detection and Analysis of the Mutation for Deafness Susceptibility Gene in Non-syndromic Hearing Loss Cases

目的:探究非综合征型耳聋患者耳聋易感基因的携带情况及突变类型,为耳聋患者治疗或遗传咨询提供理论依据。方法:收集821例非综合征型耳聋患者的外周静脉血,提取基因组DNA后,进行4个常见耳聋易感基因GJB2、GJB3、SLC26A4和线粒体12S r RNA的9个突变热点筛查。结果:821例非综合征型耳聋患者中耳聋易感基因筛查阳性375例,阳性率为45.7%,不同性别之间阳性率无明差异(P=0.625)。375例存在耳聋易感基因突变的研究对象中,4个易感基因的9突变热点共检测出447例点突变,其中GJB2基因的有241例点突变(53.9%),以235 del C位点突变率最高;SLC26A4基因的有126例点突变(28.2%),以IVS7-2 A>G位点突变为主;线粒体12S r RNA基因的有79例点突变(17.7%),绝大部分为1555 A>G位点突变;而GJB3基因仅有1例点突变(0.2%)。375例存在耳聋易感基因突变的研究对象中,304例发生1种突变(81.1%),有70例发生2种突变(18.7%),仅有1例发生3种突变(0.3%)。结论:非综合征型耳聋患者中GJB2基因的235 del C位点以及SLC26A4基因的IVS7-2 A>G位点突变率较高,常见耳聋易感基因筛查有助于非综合征型耳聋患者的诊断、干预及治疗。

Objective： To explore the deafness susceptibility gene carrier and gene mutation type in non-syndromic hearing loss cases, and provide scientific evidences for deafness patients treating and genetic counseling. Methods： A total of 821 cases of non-syndromic hearing loss were enrolled in study, and peripheral blood was collected to extract genomic DNA and detect the mutation of nine mutational hotspots of four common deafness susceptibility genes, GJB2, GJB3, SLC26A4 and mitochondrion 12S rRNA. Results： There were 375 cases with positive results of mutation for deafness susceptibility gene in 821 non-syndromic hearing loss cases. The positive rate of mutation was 45.7%, and no significant difference was found in the positive rate of mutation between male and female（P=0.625）. A total of 447 gene loci mutation was found, in nine mutational hotspots of four common deafness susceptibility genes, 375 cases carried deafness susceptibility gene. Moreover, 241 cases carried gene loci mutation of GJB2 gene （53.9%）, and 235 del C loci had the highest rate of mutation. There were 126 cases carried gene loci mutation of SLC26A4 gene （28.2%）, and the main mutation loci was IVS7-2 A 〉 G. There were 79 cases carried gene loci mutation ofmitochondrion 12S rRNA gene （17.7%）, and the highest rate of mutation came from 1555 A 〉 G loci. Only one case carried gene loci mutation ofGJB3 gene （0.2%）. Analysis of the kind of mutation for 375 cases which carried deafness susceptibility gene, and results showed that there were 304 cases with one kind of mutation （81.1%）, and 70 cases with two kind of mutation （18.7%）, but only one case with three kind of mutation （0.3%）. Conclusion： High rate of mutation for 235 del C loci of GJB2 gene, and IVS7-2 A 〉 G loci of SLC26A4 gene was found in non-syndromic hearing loss cases. Common deafness susceptibility gene screening is benefit for diagnosis, intervention and treatment of non-syndromic hearing loss cases.