内耳畸形相关SLC26A4基因的研究  

Investigation of SLC26A4 Mutations Associated with inner ear malformations

作　　者：朱庆文[1] 臧雯[2] 袁永一[3] 韩海霞[1] 张喜琴[1] 蒋新霞[1] 任秀敏[1] 冯彩红[1] 路虹[1] 

机构地区：[1]河北医科大学第二医院耳鼻咽喉科,石家庄050000 [2]石家庄市第一医院耳鼻咽喉科 [3]解放军总医院耳鼻咽喉-头颈外科

出　　处：《临床耳鼻咽喉头颈外科杂志》2012年第1期22-26,共5页Journal of Clinical Otorhinolaryngology Head And Neck Surgery

基　　金：河北省自然科学基金面上项目(No:C2010000571)

摘　　要：目的:研究内耳畸形相关SLC26A4基因在大前庭水管综合征(LVAS)、Mondini畸形及不伴前庭水管扩大的耳蜗畸形耳聋人群中的突变情况,在分子水平上探讨内耳畸形的发病机制,为基因诊断提供理论基础。方法:收集14例散发LVAS、6例Mondini畸形(伴前庭水管扩大)及7例不伴前庭水管扩大的耳蜗畸形耳聋患者的外周血DNA样本及临床资料,利用PCR扩增目的基因后直接测序的方法对所有患者进行SLC26A4基因全编码序列检测,同时进行GJB2、线粒体12SrRNA 1555/1494位点排除性检测。结果:14例LVAS患者中12例(85.7%)具有SLC26A4双等位基因(纯合或复合杂合)突变,2例(14.3%)有单等位基因突变。6例Mondini畸形患者均具有SLC26A4双等位基因(纯合或复合杂合)突变。7例不伴前庭水管扩大的耳蜗畸形耳聋患者中均未查出SLC26A4基因突变。27例患者均未发现GJB2、线粒体12SrRNA 1555/1494致病突变。结论:LVAS及Mondini畸形与SLC26A4基因突变密切相关,且Mondini畸形比单纯LVAS基因突变率更高,而不伴前庭水管扩大的耳蜗畸形耳聋患者未发现SLC26A4基因突变,尚需对该部分耳聋患者进行深入的分子病因学研究。Objective：To study the molecular pathogenesis of SLC26A4 mutations associated with inner ear malformations including large vestibular aqueduct syndrome（LVAS）,Mondini dysplasia and inner ear malformations but not accompanied with LVAS.Method：DNA sample and clinical material were obtained from 14 sporadic LVAS probands,six Mondini dysplasia probands and seven inner ear malformations excluding LVAS probands.SLC26A4 gene mutation was analyzed by direct sequencing for its 20 coding exons.GJB2 gene and also mt12SrRNA were analyzed by direct sequencing.Result：In 14 cases of LVAS,two mutations were detected in 12 patients（85.7%,either homozygous or compound heterozygous mutations）,and one mutation was found in two patients（14.3%）.In six cases of Mondini dysplasia,two mutations were detected in all of patients（100%）.No mutation could be found in the seven cases of other inner ear abnormalities not accompanied with LVAS.No pathogenic mutation was detected in all of these 27 probands in GJB2 gene and mt12SrRNA 1555/1494T.Conclusion：We have shown that LVAS and Mondini dysplasia closely correlate with SLC26A4 gene.No mutation was detected in seven probands of inner ear malformations not accompanied with LVAS.We should study the molecular pathoge-nesis of this disease in depth.

关 键 词：内耳畸形 大前庭水管综合征 MONDINI畸形 基因 

分 类 号：R764.73[医药卫生—耳鼻咽喉科]