北京地区耳聋残疾人群大前庭水管相关SLC26A4基因热点突变分子流行病学调查

Epidemiological investigation of SLC26A4 gene hot-spot mutation in patients with enlarged vestibular aqueduct among deaf population in Beijing

目的分析北京耳聋残疾人群中SLC26A4基因热点突变IVS7-2A>G和2168A>G发生频率,初步探讨SLC26A4基因热点突变在北京地区耳聋残疾人群中的分子诊断意义。方法抽查北京地区持耳聋残疾证患者6247例,均抽取外周静脉血并提取DNA,以博奥生物有限公司提供的晶芯九项遗传性耳聋基因检测试剂盒(微阵列芯片)对SLC26A4基因的热点突变IVS7-2A>G和2168A>G进行检测,并对其发生频率进行分析。结果在6247名受检耳聋残疾人群中,携带SLC26A4基因IVS7-2A>G和2168A>G突变的例数共计177例,总阳性检出率为2.83%(177/6247)。IVS7-2A>G突变携带者141例(纯合27例,单杂合突变114例),2168A>G突变携带者26例(纯合4例,单杂合突变22例),SLC26A4基因2168A>G/IVS7-2A>G复合杂合突变携带者10例。针对IVS7-2A>G和2168A>G突变的SLC26A4基因双等位基因突变例数为41例,双等位基因突变率为0.66%(41/6247)。结论 1、在6247例耳聋残疾人中,通过SLC26A4基因热点突变IVS7-2A>G和2168A>G检测能够明确分子学诊断的占总体的0.46%(41/6247);2、在北京地区持证聋人群体中,SLC26A4基因热点突变检出率较我院门诊就诊的耳聋患者低,此项课题的开展,有助于了解北京地区残疾人群中与大前庭水管综合征密切相关的SLC26A4基因热点突变分布情况,在分子水平上为耳聋残疾人群明确诊断或指导进一步诊断,并对IVS7-2A>G和2168A>G突变检测阳性患者的婚配、生育具有一定的指导意义。

Objective To study frequency of SLC26A4 genes hot-spot mutations IVS7-2 A〉G and 2168A〉G among deaf people in Beijing, to determine its value in molecular diagnosis among people with deafness. Mothods The study in- volved 6247 subjects in Beijing area with disability cards showing deafness-related disability. The genomic DNA sample was extracted from peripheral blood .The deafness SLC26A4 gene mutations of IVS7-2A〉G and 2168A〉G were distinguished by a gene test chip from CaptalBio Corporation and their frequencies analyzed. Results Among these heating disabled people in Beijing, 177 carried SLC26A4 IVS7-2 A〉G and 2168 A〉G mutations, yielding a positive detection rate of 2.83% （177/6247） and a diagnosis rate of 0.46% （41/6247）. There were 141 SLC26A4 IVS7-2 A〉G mutations carriers （27 homozygous mutation cases and 114 heterozygous mutation cases）, 26 SLC26A4 2168 A〉G mutations carriers （4 homozygous mutation cases and 22 heterozygous mutation cases） and 10 SLC26A4 2168A〉G/IVS7-2A〉G compound heterozygous mutation carriers. In 97.17%（6070/6247） of these hearing disabled persons SLC26A4 gene hot-spot mutations were not detected. Conclusions 1 .Molecu- lar diagnosis was established in 0.46% （41/6247） of this population of hearing disabled persons through testing SLC26A4 gene mutations IVS7-2 A〉G and 2168 A〉G. 2,The rate of SLC26A4 gene hot-spot mutations in Beijing area appears to be lower than among patients seen in our clinic. The study helps increase our understanding of the distribution of SLC26A4 gene hot-spot mutations in relation to enlarged vestibular aqueduct syndrome among hearing disabled people in Beijing area, im- prove diagnosis among hearing disabled people at the molecular level, and provide guidance in counseling patients with posi- tive IVS7-2 A〉G and 2168 A〉G mutations in marriage and reproduction..