TMPRSS3基因的VUS变异在1个耳聋家系中的致病性分析  

Genetics analysis for variant of uncertain significance(VUS)of TMPRSS3 gene in a family with hearing loss

作　　者：李博宇 程亚婷 王凡 邱雪平[1,2] 马建鸿 马玲 张铭 张元珍 郑芳 LI Boyu;CHENG Yating;WANG Fan;QIU Xueping;MA Jianhong;MA Ling;ZHANG Ming;ZHANG Yuanzhen;ZHENG Fang(Center for Gene Diagnosis&Department of Laboratory Medicine,Zhongnan Hospital of Wuhan University,Wuhan 430071,Hubei;Clinical Research Center of Prenatal Diagnosis and Eugenics,Wuhan 430071,Hubei,China)

机构地区：[1]武汉大学中南医院基因诊断中心&检验科,武汉430071 [2]湖北省产前诊断与优生优育临床研究中心,武汉430071

出　　处：《临床检验杂志》2023年第11期861-865,共5页Chinese Journal of Clinical Laboratory Science

摘　　要：目的针对一对耳聋夫妇和其胎儿进行家系全外显子组检测,为该家系遗传咨询提供参考和依据。方法收集该家系的临床资料,采集孕妇和其配偶的外周血和孕妇羊水,并提取基因组DNA,应用家系全外显子组测序技术进行产前遗传学检测,发现疑似致病位点进行Sanger测序验证;通过Minigene技术针对可能导致异常选择性剪切突变位点进行分析。结果孕妇携带跨膜丝氨酸蛋白酶3基因(transmembrane serine protease 3,TMPRSS3)的复合杂合疑似致病突变,孕妇配偶携带GJB2基因c.235delC的纯合致病突变。胎儿携带TMPRSS3基因复合杂合突变,分别来源于父亲的意义未明的c.323-8T>C杂合突变以及来源于母亲的c.325 C>T杂合突变;采用Minigene技术检测发现c.323-8T>C杂合突变未导致明显的剪切改变。结论TMPRSS3基因的复合杂合突变可能是导致孕妇耳聋的原因,GJB2基因纯合突变是导致孕妇配偶耳聋的原因,胎儿携带的TMPRSS3基因复合杂合突变不会导致耳聋,夫妇再生聋儿的几率很小。Objective To perform whole exome sequencing for a deaf couple and their fetus to provide genetic counseling for the family.Methods The clinical data,the samples of peripheral blood from the pregnant woman and her spouse,and amniotic fluid from the pregnant woman were collected.The genomic DNAs were extracted.The whole exome sequencing for the family was performed to find suspected pathogenic mutation sites which were verified by Sanger sequencing.Mutation sites that may lead to abnormal selective shear were analyzed by Minigene techniqueThe minigene technique was used to analyze the possible alternative splicing caused by the mutation that might induce variable splicing.Results The pregnant woman carried suspected compound pathogenic heterozygous mutations in transmembrane serine protease 3(TMPRSS3)gene,and her spouse carried pathogenic homozygous mutation c.235delC in GJB2 gene.The fetus carried compound heterozygous mutations in TMPRSS3 gene which involved in a uncertainly significant c.323-8T>C inherited from his father and a possibly pathogenic c.325 C>T inherited from his mother.The detection of minigene technology found that c.323-8T>C heterozygous mutation did not lead to obvious splicing change.Conclusion The newly discovered compound heterozygous mutations in TMPRSS3 gene and homozygous mutations in GJB2 gene may cause deafness in the pregnant woman and her spouse respectively.The compound heterozygous mutations in TMPRSS3 gene carried in the fetus does not cause deaf,thus the couple have only a slim chance for a deaf child.

关 键 词：耳聋 跨膜丝氨酸蛋白酶3基因 选择性剪切 遗传学检测 

分 类 号：R446[医药卫生—诊断学]