两个耳聋家系TMPRSS3基因突变分析及产前诊断

目的对两个耳聋家系进行遗传性耳聋基因突变检测,为家系遗传咨询与产前诊断提供参考。方法2018年3—12月,郑州大学第一附属医院遗传与产前诊断中心应用二代测序技术对两个家系患儿进行耳聋基因检测(包含168个已知致病基因,包括核基因、相关线粒体区域及miRNA),并对可疑基因在患儿及家系成员中进行Sanger双向测序验证,确定致病突变后,对两个家系的高危胎儿进行产前诊断。结果家系1患儿检测到TMPRSS3基因c.432delA和c.617-2_617-1insTC复合杂合突变,家系2患儿检测到TMPRSS3基因c.271C>T(p.R91X)和c.147dupT复合杂合突变,两家系患儿父母均为携带者。产前诊断结果显示两家系胎儿均只携带1个杂合突变。随访至2019年8月,两家系二胎分别为15月龄和13月龄,听力未见异常。结论TMPRSS3基因突变可能是两个耳聋家系的致病基因,用二代测序技术可以高效、经济准确地对遗传性耳聋患者进行基因诊断,为家系遗传咨询和产前诊断提供参考。

Mutational analysis and prenatal diagnosis of TMPRSS3 gene in two Chinese families affected with deafness

Objective To detect potential mutations in two Chinese families affected with deafness,so as provide prenatal diagnosis for them.Methods Two Chinese families affected with deafness were identified at the genetic and prenatal diagnosis center of the First Affiliated Hospital of Zhengzhou University from March 2018 to December 2018.Mutation analyses were carried out by next generation sequencing(NGS),suspected mutations were verified by Sanger sequencing in the probands,unaffected relatives.Prenatal diagnosis for high-risk fetus were carried out through Sanger sequencing.Results The proband of family 1 carried a c.432delA and a c.617-2_617-1insTC mutation of the TMPRSS3 gene,the proband of family 2 carried a c.271C>T(p.R91X)and a c.147dupTmutation ofthe TMPRSS3 gene,both parents of the two probands were carriers of heterozygous variants.Conclusions Mutations in the TMPRSS3 gene are the suspected cause of deafness in two families.Application of next generation sequencing technologies make gene diagnosis of deafness efficiently and accurately and the molecular findings increase our understanding of the function of TMPRSS3 gene and enrich the human gene mutation database.It is helpful for recurrent genetic counseling and prenatal diagnosis for these families.