感音神经性耳聋患者大前庭导水管综合征相关SLC26A4基因IVS7-2A＞G的全序列分析  

Sequencing analysis of whole SLC26A4 gene in severe to profound sensorineural hearing loss patients with IVS7 --2A〉G mutation of the gene

作　　者：李琦[1,2] 黄德亮[3] 朱庆文[3] 袁永一[3] 方如平[1] 戴朴[3] 

机构地区：[1]南京医科大学附属南京儿童医院耳鼻咽喉-头颈外科,210008 [2]南京医科大学附属南京儿童医院儿童听力中心,210008 [3]中国人民解放军总医院耳鼻咽喉-头颈外科

出　　处：《中华医学遗传学杂志》2010年第6期610-615,共6页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金（30572015）;南京市医学科技发展基金重点项目（ZKX09009）

摘　　要：目的 对携带SLC26A4基因IVS7-2A＞G单杂合突变感音神经性耳聋患者进行 SLC26A4基因的全序列检测,以期发现除IVS7-2A＞G以外的其他突变.方法 应用直接测序法对80例携带IVS7-2A＞G单杂合突变的感音神经性耳聋患者进行SLC26A4基因进行全序列测序.结果 80例患者中47例发现另1个突变位点,其余33例未发现复合杂合突变,IVS7-2A＞G单杂合突变找到另外1个突变的比例为58.8%（47/80）.发现了 3个新的突变,分别是5＋2T＞A、14-2A＞G和1825del G,最为常见的5种突变为H723R（20%）、T410M（5%）、15＋5G＞A（5%）、L676Q（5%）、N392Y（3.75%）.第17外显子是突变发生种类最多的外显子.结论 SLC26A4基因IVS7-2A＞G单杂合突变者应该进行其他突变的筛查,SLC26A4基因复合突变可以解释部分的耳聋原因.Objective To investigate the whole sequence of the SLC26A4 gene in moderate to profound sensorineural hearing loss （SNHL） patients with IVS7-2A〉G mutation of the gene in China.Methods Whole SLC26A4 gene sequence was analyzed by direct sequencing in 80 SLC26A4 gene IVS7-2A〉G mutation carriers for the occurrence of a second mutation in the gene. Results Forty-seven out of the 80 patients were found to have a second heterozygous mutation, whereas a single IVS7- 2A〉 G mutation could be responsible for SNHL in the remaining 33 patients. Three novel mutations, 5＋ 2T〉A,14-2A〉G and 1825del G, were identified. The five most common mutations include H723R （20%）,T410M （5%）, C. 1705＋5G〉A （15＋5G〉A） （5%）, L676Q（5%）, and N392Y （3. 75%）. Exon 17 harbored the most types of compound heterozygosity with the IVS7 - 2A〉G mutation. Conclusion A Chinese specific SLC26A4 diversity was found, and comparable SLC26A4 contributing to deafness. This study suggested that if a heterozygous SLC26A4 mutation is found in a patient with deafness, other exons of the SLC26A4 gene should be analyzed. Furthermore, double heterozygosity of theSLC26A4 gene may also account for some of the disease phenotype.

关 键 词：SLC6A4基因 耳聋 突变谱 中国人 基因序列分析 

分 类 号：R686[医药卫生—骨科学]