上海地区35例大前庭导水管综合征相关耳聋患者常见致病基因的分子诊断研究  

Molecular diagnosis of SLC26A4, FOXI1 and KCNJ10 gene in 35 Shanghai probands with non-syndromic hearing loss associated with enlarged vestibular aqueduct

作　　者：柴永川[1,2] 李晓华[1,2] 李磊[1,2] 李幼瑾[3] 吕静荣[1,2] 李蕴[1,2] 马衍[1,2] 陶峥[2,3] 杨涛[1,2] 吴皓[1,2] 

机构地区：[1]上海交通大学医学院附属新华医院耳鼻咽喉-头颈外科,上海200092 [2]上海交通大学耳科学研究所,上海200092 [3]上海交通大学医学院附属上海儿童医学中心耳鼻咽喉科,上海200127

出　　处：《诊断学理论与实践》2010年第5期437-442,共6页Journal of Diagnostics Concepts & Practice

基　　金：上海市科委重大项目(08DZ1980100);上海市科委项目(08XD1402900);国家自然科学基金面上项目(30971596);上海市科学技术委员会重大基础研究项目(09DJ1400604)

摘　　要：目的:探讨上海地区大前庭导水管(EVA)综合征相关耳聋患者常见致病基因SLC26A4、FOXI1、KCNJ10及SLC26A4启动子c.-103位点的突变情况,在分子水平上明确该病的发病机制和诊断基础。方法:收集上海地区35例散发EVA综合征耳聋患者的外周血DNA样本及临床资料,利用巢式PCR扩增目的基因后直接测序的方法,对所有患者进行主要致病基因SLC26A4全编码序列及侧翼序列的检测,并针对无SLC26A4双等位基因突变的患者继续进行SLC26A4基因启动子c.-103位点、FOXI1和KCNJ10基因的突变检测。应用Sequencher4.9软件对上述测序结果进行分析。结果:23例(66%)和4例(11%)先证者分别具有SLC26A4双等位基因(纯合或复合杂合)和单等位基因突变。SLC26A4基因共有13种突变被检出,其中c.919-2A>G突变和p.R409H突变分别占总检出突变的64%(32/50)和8%(4/50)。8例(23%)先证者未检出SLC26A4基因突变。在无SLC26A4双等位基因突变的全部12例(34%)患者中,未检测出SLC26A4基因启动子c.-103位点、FOXI1和KCNJ10基因突变。结论:与已报道中国EVA综合征耳聋人群基因诊断数据相比,上海地区患者SLC26A4基因突变率明显偏低,体现出中国地域性人群遗传结构上的差异;其他报道致病基因FOXI1、KCNJ10及SLC26A4启动子c.-103位点突变不构成上海地区EVA综合征耳聋患者的主要病因。Objective To elucidate the molecular pathogenesis of non-syndromic hearing loss associated with enlarged vestibular aqueduct （EVA） in Shanghai, China by mutation screening of SLC26A4, FOXI1, KCNJ10 and SLC26A4 promoter c.-103 site. Methods DNA sample and clinical material were obtained from 35 unrelated EVA probands in Shanghai. The exons and the flanking splicing sites of SLC26A4 were screened in all probands by nested PCR and direct sequencing. Probands with zero or one mutation in the SLC26A4 coding region were further screened for FOXI1, KCNJ10 and SLC26A4 promoter c.-103 site. Results Twenty-three （66%） and 4 （11%） probands carried biallelic and monoallelic mutations of the SLC26A4 gene, respectively. A total of 13 types of SLC26A4 mutations were identified, with c.919-2AG and p.R409H mutations accounting for 64% （32/50） and 8% （4/50） of mutatant alleles, respectively. No mutation was detected in 8 （23%） probands. In all 12 （34%） probands with zero or one SLC26A4 mutation, no mutation was detected in FOXI1, KCNJ10 and SLC26A4 promoter c.-103 site. Conclusions Compared with previous reports concerning Chinese EVA patients, our results shows a significantly lower percentage of EVA patients in Shanghai having SLC26A4 mutations. This discrepancy indicates the genetic structure of Chinese population varies in different regions. We also shows that mutation in FOXI1, KCNJ10 and SLC26A4 promoter c.-103 site is not the major cause of EVA in Shanghai. Our study provided valuable information for the molecular diagnosis of EVA in Shanghai population.

关 键 词：大前庭导水管综合征 耳聋 SLC26A4基因 FOXI1基因 KCNJ10基因 

分 类 号：R764.43[医药卫生—耳鼻咽喉科]