浙江省余姚地区22个非综合征型耳聋家系遗传分析

The genetic analysis of patients with non-syndrome deafness come from twenty-two families in Yuyao,Zhejiang province

目的:对宁波市余姚地区22个非综合征型耳聋(NSHI)家系GJB2、GJB3、GJB6编码区以及线粒体基因突变分析,进行临床、遗传和分子特征分析评估。方法:调查对象来自于余姚市人民医院22个NSHI家系22名先证者及患病家属33名,听力正常者254例,且均未携带GJB2、GJB3、GJB6编码区以及线粒体基因致病突变。所有受检者均采集外周血并提取DNA,并对受检者GJB2、GJB3、GJB6基因编码区以及线粒体基因进行测序,结合患者听力学检查、耳聋相关突变热点基因检测以及患者家系资料进行综合遗传分析。结果:在来源于宁波市余姚地区的22个NSHI家系的33名患者中,发现携带有GJB2基因235del C单突变家系4例,GJB2双杂合突变家系2例,线粒体基因1555位点突变3例。在GJB3、GJB6编码区并未发现有致病突变。在这22个NSHI患者家系中,有27.3%的家系检测出携带有GJB2基因病理性突变;有13.6%的家系携带有线粒体12S r RNA基因1555A>G突变。据临床资料显示,6个携带GJB2基因病理性突变家系以及3个携带1555A>G突变家系的听力损失程度、发病年龄、耳聋外显率等都有差异。结论:GJB2基因以及线粒体12S r RNA基因1555A>G突变是浙江省余姚地区NSHI患者的主要相关基因,可能也存在其他未知基因与这2个基因相互协同作用,对患者表型产生影响。

Objective： To explore the clinical, genetic and molecular characteristics of twenty-two familieswith non-syndrome deafness in Yuyao area. This study focused on analyzing mutations of mitochondrial gene andcoding sequence of GJB2, GJB3, GJB6 gene. Methods： The samples were 33 patients with non-syndrome deafnesscome from 22 families in YuYao People’s hospital, and 254 cases with normal hearing. DNA were extractedout from peripheral blood of all subjects. All samples’ GJB2, GJB3 and GJB6 gene encoding region and mitochondrialgene were analyzed by direct sequencing, audiological examination, genetic testing for deafness andpedigree data. Results： The sequencing results revealed that 4 families carried GJB2 235delC mutation, 2 familiescarried GJB2 compound heterozygous mutations accounted for 27.3% and 3 families carried mitochondrial12S rRNA A1555G accounted for 13.6% in the 22 families with non-syndrome deafness. All families withoutpathogenic mutations in the GJB3 and GJB6 encoding region. According to clinical data, 6 families with GJB2gene mutations and 3 families with 1555A〉G mutations had different levels in hearing loss, age of onset, andthe rate of hearing loss. Conclusion： GJB2 and mitochondrial 12S rRNA 1555A〉G gene mutation are the maingenetic inheritance for the patients with non-syndrome deafness in Yuyao area, there may also be other unknowngenes or environmental factors to coordinated with GJB2 gene and mitochondrial 12S rRNA gene co-modulatethe variable penetrance and expressivity of deafness.