广西壮族自治区23个非综合征型耳聋家系分子遗传病因分析

Analysis of deafness-related gene mutations in 23 nonsyndromic hearing impairment families in Guangxi Zhuang Autonomous Region

目的:分析广西地区23个非综合征型耳聋家系耳聋基因的突变特点,了解广西地区该疾病的分子流行病学特点。方法:研究对象为广西地区23个非综合征型耳聋家系中的患者及其血缘家属共66例(家系组),另取散发NSHL患者及血缘亲属共167例作为对照组,用遗传性耳聋基因芯片联合DNA测序方法检测及分析家系组先证者、耳聋者、正常听力者的常见耳聋基因突变情况,分析广西地区可能的多发位点及罕见位点。结果:家系组常见耳聋基因突变率(31.82%)高于对照组(11.38%),其中GJB2突变21.21%,SLC26A4突变9.09%均高于对照组(GJB2 5.99%、SLC26A4 3.59%)。耳聋家系的先证者、耳聋患者、听力正常的亲属耳聋基因检出率均高于对照组(均<0.05)。进行常见耳聋基因全序列分析的家系中检测到SLC26A4IVS11+47T﹥C、1548insC和GJB2 235delC/109A>G 3个罕见的突变位点。结论:GJB2和SLC26A4是广西地区非综合征型耳聋家系最常见的突变基因,家系分析有助于判断突变与疾病的关系。

Objective：To investigate the genetic characteristics of the mutations responsible for nonsyndromic hearing loss in Guangxi Zhuang Autonomous Region,and analyze the deafness-related gene mutations in nonsyndromic hearing impairment families in this region.Method：In 23 nonsyndromic hearing impairment families,66 patients or their families were enrolled as family history group and 167 patients or their families without family histiory as control group,respectively.Deafness gene mutations were determined with deafness-related gene mutations detection kits.The mutation rates among the deafness probands,the hearing impairment patients and their audibility relatives were analyzied.Whole length sequences of the deafness-related gene were detected if there was mutation by the kits,to explore Guangxi region-specific mutation-sites.Result：Common deafness-related gene mutation rate in family history group（31.82%）was higher than that in control group（11.38%）,including those that in GJB2homozygous（21.21%）,SLC26A4homozygous（9.09%）,both were higher than the control group（GJB2homozygous 5.99%,SLC26A4 homozygous 3.59%）.The rate of common deafness-related gene mutations in the deafness probands was 34.78%,in the hearing impairment patients was 30.56%,in their audibility relatives was29.63%,all of which were higher than those in the control group.We found three rarely seen mutations,SLC26A4IVS11＋47T〉C,1548 insC and GJB2 109A〉G,by detecting the whole-length sequences of the deafness-related gene.Conclusion：The results indicated that GJB2 and SLC26A4were the most frequent mutant genes in Guangxi region.Analysis of the individual family were helpful to linkage the mutations and the deafness.