间隙连接蛋白基因与遗传性聋的相关性研究  

Study of the relation between Cx31 gene and hereditary hearing impairment

作　　者：高为华[1] 柯肖枚[1] 刘玉和[1] 朱平[2] 潘凯枫 

机构地区：[1]北京大学第一医院耳鼻咽喉头颈外科,100034 [2]北京大学遗传中心 [3]北京大学肿瘤医院流行病研究室

出　　处：《中华耳鼻咽喉科杂志》2004年第6期344-348,共5页Chinese Journal of Otorhinolaryngology

基　　金：北京大学 985项目人类疾病中心基金资助 ( 2 0 0 0 A 10 )

摘　　要：目的　分析中国人无综合征耳聋的间隙连接蛋白 (Connexin31,Cx31)基因突变及突变频率和特性 ,从分子水平探讨该病的发病机理。方法　收集中国人 4 7例无综合征耳聋家系先证者 ,38例散发的无综合征耳聋患者以及 10 0例健康对照 ,应用聚合酶链反应 (polymerasechainreaction ,PCR)扩增Cx31基因编码区片段 ,通过变性高效液相色谱法 (denaturinghigh performanceliquidchromatography ,DHPLC)筛查突变 ,经DNA测序证实突变。结果　Cx31基因编码区 798C→T杂合突变在耳聋患者和健康对照组发生率分别为 14 1% (12 / 85 )和 1% (1/ 10 0 ) ,两者间差异具有非常显著性意义 (P <0 0 1)。在一个常染色体显性无综合征耳聋家系中的 2例患者发现Cx31基因编码区 5 80G→A杂合突变 ,导致A194T的错义突变 ,家系中听力正常者及健康对照无此突变。在 1例散发无综合征耳聋患者Cx31基因的编码区 ,发现 2 5 0G→A杂合突变。此外 ,本科题组以往已经对本实验中的耳聋家系及散发耳聋患者和对照筛查了Cx2 6基因突变 ,并发现 2个家系存在Cx2 6基因突变。但本实验在这 2个Cx2 6基因突变引起的无综合征耳聋家系未筛查到Cx31基因突变。而Cx31基因突变者也不存在Cx2 6基因突变。结论　Cx31基因与无综合征耳聋相关 。Objective To study the relation between hereditary nonsyndromic hearing impairment (NSHI) in Chinese and mutation in Connexin 31 (Cx31) gene and to explore the pathogenic mechanism. Methods Forty-seven pedigrees with hereditary NSHI, 38 Children with sporadic NSHI and cases of control were collected in present studies. The coding sequence of Cx31 gene was amplified by polymerase chain reaction (PCR), screened by denaturing high-performance liquid chromatography (DHPLC) and confirmed by direct sequencing. Results The mutation rate of heterozygous mutation C→T at position 798 of Cx31 cDNA in patient group and in control were 14.1%(12/85) and 1%(1/100) respectively. Significant difference was found between the two group(P<0.01). Heterozygous mutation G→A at position 580 of GJB3 cDNA, which results in a missense mutation (A194T) , was found in two members of one pedigree with autosomal dominant NSHI. The mutation was not found in numbers with normal hearing of this pedigree and controls. Heterozygous mutation G→A at position 250 of Cx31 cDNA was found in one child with sporadic congenital NSHI.In our previous studies, Cx26 gene mutations have been screened among the patient with hereditary NSHI and sporadic NSHI and the control of our test,and two Cx26 gene mutations were found in two pedigrees. But the two NSHI pedigrees which were confirmed to have Cx26 gene mutation were not found to have Cx31 mutation. The patient and the control which were confirmed to have Cx31 gene mutations were not found to have Cx26 mutations. Conclusions Cx31 gene was associated with nonsyndromic hearing impairment. There was no cross and cooperative effect between Cx26 gene and Cx31 gene.

关 键 词：间隙连接蛋白基因 遗传性聋 基因突变 发病机理 

分 类 号：R764[医药卫生—耳鼻咽喉科]