国人非综合征型遗传性聋患者GJB3基因突变分析

Mutation Analysis of GJB3 in Chinese Population with Non-syndromic Hearing Impairment

目的 研究GJB3基因[编码缝隙连接蛋白31(Cx31) ]突变在国人耳聋患者中的特征。方法 应用聚合酶链反应(PCR)产物直接测序方法对各种感音神经性聋患者及家属14 1名、对照组15 0名进行GJB3基因编码区突变检测及鉴定。结果 在14 1名患者中发现GJB3基因的三种单核苷酸改变,其中有两种碱基变化导致了氨基酸的改变,为错义突变方式。其中一个突变( 5 4 7G→A)与夏家辉等报道相同;另一个突变形式( 2 5 0G→A)为本研究首次发现,且进一步的各物种多种连接蛋白氨基酸序列进化分析证实该突变位点位于Cx31高度保守的第二跨膜区。15 0名正常对照组中未发现同样突变。结论 国人非综合征型遗传性聋者GJB3基因突变筛查研究发现了一个GJB3基因新的突变形式( 2 5 0G→A) ,为进一步开展耳聋相关基因的筛查研究打下了基础。

Objective To investigate the contribution of the GJB3 gene (encoding connexin 31) mutations in Chinese population with sporadic non-syndromic hearing impairment. Methods PCR were performed with one pair of primer in the coding sequence of GJB3 gene.Bidirectional sequencing of PCR products was subsequently applied in 141 patients with hearing loss and 150 normal controls.Results Two different single base pair changes were detected: 547G→A and 250G→A.Two patients carried two kinds of mutation.547G→A mutation was reported before.The other was a novel mutation-250G→A, resulted in amino acid change, V84I. This mutation was not detected in the control subjects. The valine with alteration residue lied within the second conserved transmembrane domain.Conclusion The discover of the novel mutation (250G→A) can help GJB3 screening in the patients with hearing impairment in the future.