135例大前庭导水管耳聋患者SLC26A4基因突变分析

摘要

Objective To investigate the mutation spectrum of SLC26A4 and to elucidate molecular mechanisms un-derlying non-syndromic hearing loss associated with enlarged vestibular aqueduct in east China by screening for SLC26A4 gene mutations.Methods Blood samples and clinical data were collected from 135 unrelated EVA probands and screening of coding regions of the SLC26A4 gene was performed by nested polymerase chain reaction followed by Sanger sequencing.Results One hundred(74.07%)probands carried two SLC26A4 mutant alleles and ten(7.41%)had one SLC26A4 mutant allele, while no mutation was detected in the rest twenty-five (18.52%) patients.A total of 51 types of SLC26A4 mutations were identified with c.919-2A>G and p.H723R being the most common mutations account-ing for 50%(105/210)and 10.48%(22/210)of mutant alleles,respectively.Conclusions Consistent with previous re-ports,c.919-2A>G is most prevalent in Chinese.Further research will be needed to investigate other genetic factors that may contribute to the pathogenesis of EVA given the fact that a large percentage of patients lack mutations in the SLC26A4 coding region in one or both alleles.%目的 研究华东地区非综合征性大前庭导水管耳聋患者SLC26A4基因的突变情况,以进一步了解其突变谱,为阐明EVA的分子机制和指导基因诊断提供依据.方法 通过巢式聚合酶链式反应扩增目的片段和Sanger测序对135例明确诊断的散发非综合征性EVA耳聋患者SLC26A4基因的外显子及侧翼序列进行变异检测.结果 在135例EVA耳聋患者中,明确为SLC26A4双等位基因突变致病的占74.07%(100/135),单等位基因突变的占7.41%(10/135),18.52%(25/135)的患者未检测到任何SLC26A4基因突变.共检出51种SLC26A4基因突变,其中, c.919-2A>G突变和p.H723R突变最常见,分别占总检出突变的50%(105/210)和10.48%(22/210).结论 与既往报道一致,c.919-2A>G突变为中国人群SLC26A4基因的最常见变异.有相当一部分患者未检出SLC26A4双等位基因突变,提示可能有其他致病因子参与EVA的发生,有待进一步研究阐明.