育龄期夫妇非综合征性耳聋基因突变位点检测结果分析  

Analysis on non-syndromic hearing loss gene mutation sites in couples of reproductive age

作　　者：柳红杰[1] 刘日明[2] 丛江琳[1] 马莉[2] 王晓黎[1] 王宁[2] 曲鑫[1] 于晓艳[1] 李淑红[1] 王哲[2] 孙成铭[2] 

机构地区：[1]青岛大学医学院附属烟台毓璜顶医院妇产科,烟台264000 [2]青岛大学医学院附属烟台毓璜顶医院检验科,烟台264000

出　　处：《中华生物医学工程杂志》2016年第3期194-199,共6页Chinese Journal of Biomedical Engineering

基　　金：炯台市科学技术发展计划（2012089）

摘　　要：目的：探讨听力正常的育龄期夫妇进行中国人群常见非综合征性耳聋的分子流行病学数据。方法选取2012年6月至2015年2月在本院正常产检听力正常孕妇5338例（24-45岁），携带耳聋基因突变孕妇的听力正常配偶236例（24-42岁），抽取静脉血并提取基因组DNA。采用基因芯片技术对中国人群常见的4个耳聋基因GJB2、GJB3、SLC26A4及线粒体12S rRNA进行筛查；对携带耳聋基因突变孕妇的配偶进行相应基因测序；对夫妻双方均为同一等位基因突变携带者的孕妇进行羊水穿刺做产前诊断。结果 5338例听力正常孕妇中有319例（5.98%，319/5338）检出耳聋基因突变，其中GJB2基因172例（3.22%，172/5338）、GJB3基因26例（0.48%，26/5338）、SLC26A4基因114例（2.14%，114/5338）和线粒体12S rRNA基因13例（0.24%，13/5338）；有3例孕妇检出非等位基因的2个耳聋基因突变位点。236例携带耳聋基因突变孕妇的听力正常配偶（GJB2突变132例、SLC26A4突变104例）中7例（2.96%，7/236）携带耳聋基因突变，GJB2基因3例（1.27%，3/236）、SLC26A4基因4例（1.70%，4/236）。夫妻双方均为同一等位基因突变携带者的7例孕妇中1例确诊为GJB2等位基因内部双杂合突变，另1例确诊为SLC26A4等位基因内部双杂合突变。结论 GJB2的235delC和SLC26A4的IVS7-2A〉G突变率位列本地区育龄期夫妇非综合症耳聋基因突变的前两位。对这些位点的筛查能有效降低先天性聋儿的出生率。Objective To investigate the molecular epidemiology data on non-syndromic hearing loss（NSHL）,a common hearing disorder in Chinese,among normal-hearing couples of reproductive age. Methods Included in this study were 5 338 normal-hearing pregnant women（aged 24 to 45 years old）who underwent routine prenatal examination in our hospital between June 2012 and February 2015,and 236 normal-hearing spouses（aged 24 to 42 years）of those found to bear deafness gene mutations. Venous blood samples were collected from these subjects for extraction of DNA genome. Using gene microarry ,we screened for mutants of 4 deafness genes（GJB2,GJB3,SLC26A4 and mitochondrial 12S rRNA）which are frequently found in Chinese population. Gene sequencing of these sites were performed for spouses of pregnant women who carried deafness gene. Of couples who carried mutant on a same allele,the pregnant wives underwent amniocentesis for prenatal diagnosis. Results Of the 5 338 normal-hearing pregnant women,319（5.98%, 319/5 338）were detected to have deafness gene mutations,including 172 at GJB2（3.22%,172/5 338）,26 at GJB3（0.48%,26/5 338）,114 at SLC26A4（2.14%,114/5 338）and 13 at mitochondrial 12S rRNA （0.24%,13/5338）. Three pregnant women were found to have 2 deafness gene mutation sites located on non-alleles. Among normal-hearing spouses of 236 women found to have deafness gene mutations（132 with GJB2 mutation and 104 with SLC26A4 mutation）,7（2.96%7/236）also had deafness gene mutations,including 3 at GJB2（1.27%,3/236）and 4 at SLC26A4（1.70%,4/236）. Of 7 couples who carried mutant on a same allele,one pregnant woman was found to have double heterozygous mutation at GJB2,and another have double heterozygous mutation at SLC26A4. Conclusion The rates of gene mutants 235delC at GJB2 and IVS7-2A〉G at SLC26A4 rank the first two leading gene mutations for NSHL among couples of reproductive age in Qingdao. Screening for these mutation sites can effectively reduce the birth rate of congenital deaf children.

关 键 词：遗传性耳聋 基因诊断 遗传咨询 产前诊断 

分 类 号：R764.43[医药卫生—耳鼻咽喉科]