产前序贯性筛查遗传性耳聋基因携带者的临床意义分析  

Analysis on the clinical significance of prenatal sequential screening for hereditary deafness gene carriers

作　　者：李珊珊[1] 张萌[1] 陈玉娇 闫有圣 王一鹏[1] LI Shanshan;ZHANG Meng;CHEN Yujiao;YAN Yousheng;WANG Yipeng(Prenatal Diagnostic Center,Beijing Obstetrics and Gynecology Hospital,Capital Medical University·Beijing Maternal and Child Health Care Hospital,Beijing 100026,China)

机构地区：[1]首都医科大学附属北京妇产医院/北京妇幼保健院产前诊断中心,北京100026

出　　处：《中国临床新医学》2024年第7期765-771,共7页CHINESE JOURNAL OF NEW CLINICAL MEDICINE

基　　金：北京市研究型病房示范建设单位项目(编号:BCRW202109)。

摘　　要：目的分析产前序贯性筛查遗传性耳聋基因携带者的临床意义。方法选择2022年5月至12月于首都医科大学附属北京妇产医院进行遗传性耳聋基因突变位点筛查的孕妇9391例,采用微流控芯片法检测遗传性耳聋基因,分析其在孕妇人群中的携带率。对检出GJB2基因和SLC26A4基因变异的孕妇配偶采用靶向高通量测序进行相同致病基因筛查,当夫妻双方均检出同一基因致病变异时建议对胎儿进行致病基因的产前诊断。对于检出GJB3基因变异孕妇,建议其进行听力学评估和遗传咨询及随访。对检出线粒体12S rRNA基因变异孕妇进行遗传咨询及用药指导。结果9391例孕妇中检出遗传性耳聋基因突变携带者1002例,携带率为10.67%;GJB2、SLC26A4、GJB3及线粒体12S rRNA突变的携带率分别为7.93%、1.99%、0.28%和0.15%。突变经Sanger测序验证,符合率达99.80%。293例GJB2基因或SLC26A4基因突变携带者的配偶进行了序贯性筛查,其中4对夫妇双方检出携带相同基因上的致病突变位点,经羊水细胞测序,1例为GJB2 c.235 del C纯合突变,1例为SLC26A4 c.919-2 A>G纯合突变,其余2例均为杂合突变。结论产前序贯性筛查耳聋基因携带者不仅可以筛查遗传性耳聋基因突变的携带者,还可以发现药物性耳聋敏感性个体,从而实现耳聋胎儿早期诊断、早期干预和及时预警。Objective To analyze the clinical significance of prenatal sequential screening for hereditary deafness gene carriers.Methods A total of 9391 pregnant women who underwent mutational site screening for hereditary deafness genes in Beijing Obstetrics and Gynecology Hospital,Capital Medical University from May 2022 to December 2022 were selected.The hereditary deafness genes were detected by using microfluidic chip method and the carrying rate of these hereditary deafness genes in the pregnant women was analyzed.The spouses of the pregnant women with GJB2 gene and SLC26A4 gene variants detected were screened for the same pathogenic genes by using targeted high-throughput sequencing.When both sides of the spouses were detected with the same pathogenic gene variants,prenatal diagnosis of the pathogenic gene was recommended for their fetus.For the pregnant women with GJB3 gene variant,audiological evaluation,genetic counseling and follow-up were recommended.For the pregnant women with mitochondrial 12S rRNA gene variant detected,genetic counseling and medication guidance were provided.Results Among the 9391 pregnant women,1002 cases were found to be carriers of hereditary deafness gene mutation,and the carrying rate was 10.67%.The carrying rates of GJB2,SLC26A4,GJB3 and mitochondrial 12S rRNA mutations were 7.93%,1.99%,0.28%and 0.15%,respectively.The mutations were verified by Sanger sequencing and the coincidence rate was 99.80%.The spouses of 293 carriers of GJB2 gene or SLC26A4 gene mutations were screened sequentially.Among these spouses,4 couples were found to carry the disease-causing mutation site of the same gene.After sequencing of amniotic fluid cells,1 case was found to carry GJB2 c.235 del C homozygous mutation,and 1 case was found to carry SLC26A4 c.919-2 A>G homozygous mutation and the other 2 cases were found to carry heterozygous mutations.Conclusion Prenatal sequential screening of deafness gene carriers can not only screen the carriers of hereditary deafness gene mutations,but also identify the indivi

关 键 词：遗传性耳聋基因 微流控芯片 产前筛查 遗传咨询 

分 类 号：R714.55[医药卫生—妇产科学]