中文摘要：

目的在全国27个省市聋校学生2352例中进行基于SLC26A4基因热点突变IVS7-2A〉G的该基因的全序列筛查,分析和探讨中国人SLC26A4基因相关大前庭水管综合征的分子流行病学状况。方法调查对象来自全国27个省市自治区的聋哑学校学生2352例,共涉及21个民族。听力正常的对照人群150例。所有受检者均采集外周血并提取DNA,其中1552例以序列分析方法检测SLC26A4基因外显子7＋8以筛查热点突变IVS7-2A〉G,800例以试剂盒的方法检测IVS7-2A〉G突变。对携带IVS7-2A〉G纯合突变的个体结束筛查,对携带IVS7-2A〉G单杂合突变的个体进行SLC26A4基因其他外显子测序,寻找可能存在的另外一个突变位点。结果 2352例来自全国多个地区的耳聋患者中271例携带SLC26A4基因IVS7-2A〉G突变,其中106例携带IVS7-2A〉G纯合突变,165例携带IVS7-2A〉G单杂合突变,IVS7-2A〉G突变总检出率达到11.52%（271/2352）,汉族患者中IVS7-2A〉G突变检出率达到13.35%（254/1903）;对165例携带IVS7-2A〉G单杂合突变的患者进行SLC26A4基因其他外显子序列分析显示其中105例找到另外一个突变位点,其余60例未找到另外的突变。2352例耳聋患者中基于IVS7-2A〉G突变的SLC26A4基因纯合及复合杂合突变携带者共211例,占总人数的8.97%（211/2352）。其中1903例汉族耳聋患者中基于IVS7-2A〉G突变的SLC26A4基因纯合及复合杂合突变携带者共199例,占汉族人数的10.46%（199/1903）。105例携带SLC26A4基因复合杂合突变的患者中,除IVS7-2A〉G突变外的另一突变位点主要存在于外显子19、10、17、11＋12、3和15上。正常对照人群IVS7-2A〉G突变检出率为2%,均为单杂合突变,且均未找到另一个突变。结论 2352例聋哑学生通过基于SLC26A4基因热点突变IVS7-2A〉G的该基因的全序列筛查,将211例耳聋患者明确为SLC26A4基因突变致聋;发现在中国由SLC26A4基因热点突变引起的大前庭水管相关遗传性

英文摘要：

Objective To gather molecular epidemiological data on association between the SLC26A4 gene and enlarged-vestibular-aqueduct-syndrome related hearing loss in China with a focus on the hot spot mutation IVS 7-2 A〉G. Methods DNA were extracted from peripheral blood of 2 352 students from deaf and dumb schools in 27 different regions across China. The ethnic ity of the 2352 subjects covered Han （n = 1903）, Tibetan （n = 119）, Uygur （n = 69）, Hui （n = 89）, Mongolian （n = 33）, Yi, Zhuang, Bai, Miao and 12 other minority groups （n = 139）. Of these subjects, 1 552 were screened for the hot spot mutation IVS 7-2 A 〉G by direct sequencing, and 800 were screened by the Genetic Testing Kit. Those carrying a single heterozygous IVS 7-2 A〉G were further tested for a possible second mutation on the SLC26A 4 gene in exons other than exons 7 and 8. One hundred and fifty normal hearing individuals served as the control group. Results There were 271 IVS 7-2 A 〉G carriers, of whom 106 were homozygous carriers and 165 were heterozygous carriers. Of the 165 heterozygous IVS 7-2 A〉G carriers, 105 were found to have another mutation on the SLC26A4 gene. The rate of homozygous and compound heterozygous IVS 7-2 A〉G mutations was 8.97% for the entire study population （211/2352）, and 10.46% for the Hans （199/1903）. In the 105 eases with SLC26A4 compound heterozygous mutations, the non-IVS 7-2 A〉G mutations were found mainly in exons 19, 10, 17, 3, 11＋12 and 15. Only 2 heterozygous IVS 7-2 A〉G carriers were found in the control group, with no other SLC26A4 gene mutations. Conclusion Whole SLC26A4 gene analysis with focus on IVS7-2A〉G mutation showed that 211 of the 2352 deaf students had SLC26A4 gene related mutations. SLC26A 4 mutations account for about 9% of enlarged-vestibular-aqueduct-syndrome related hereditary hearing loss in China. It＇s of great importance to screen SLC26A4 gene for etiological diagnosis in deafness. This study also provides preliminary evidence of hot spot areas o