非综合征型耳聋家系的产前诊断和遗传咨询

Prenatal diagnosis and genetic counseling in families with non-syndromic hearing loss

目的评估耳聋高危家庭产前诊断和遗传咨询方案的准确性和有效性。方法对80例非综合征型耳聋患儿使用PCR导流杂交法进行耳聋基因筛查,检测出21例携带耳聋基因突变,分别包含4个热点基因GJB2、GJB3、SLC26A4及12SrRNA的16种突变位点。21例耳聋基因突变家系及1例耳聋筛查阴性家系和1例有耳聋家族史家系均有生育需求需要进行产前诊断。根据各家系耳聋先证者基因检测突变位点、家族遗传史及用药史,设计Sanger测序引物,对23个家系中91个家系成员进行检测并提供遗传咨询及优生指导。出生后听力随访,予以评估产前诊断与遗传咨询方案的准确性和有效性。结果80例耳聋患儿中筛查出21例携带耳聋基因突变。产前诊断23例胎儿发现:7例野生型、6例单杂合突变,2例双基因杂合突变,2例GJB2双杂合突变(235delC/79G>A、235delC/341A>G),5例单基因双杂合突变及1例GJB2/SLC26A4:35delG/176del16/439双基因双杂合突。经遗传咨询,5例单基因双杂合突变及1例双基因双杂合突变(GJB2/SLC26A4:35delG/176del16/439)诊断为耳聋,这6例胎儿均已引产。7例野生型胎儿及6例单杂合突变,2例双基因杂合突变,2例GJB2双杂合突变,共17例可继续妊娠。这17例胎儿出生后随访5年,听力一直正常。结论产前诊断和遗传咨询方案为高危耳聋家庭提供了详细的指导信息,可以有效减少高危聋儿的出生,具有很好的应用价值。

Objective To evaluate the accuracy and effectiveness of protocol for prenatal diagnosis and genetic counseling for families at high risk of hearing loss.Methods A total of 80 cases with non-syndromic hearing loss(NSHL)were screened by PCR reverse hybridization.A total of 21 cases were detected with deafness gene mutations,including 16 mutation sites of 4 hot genes GJB2,GJB3,SLC26A4 and 12SrRNA.Twenty-one cases with deafness gene mutation families,1 case with deafness gene screening negative family and 1 case with a family history of deafness all had fertility needs and required prenatal diagnosis.According to the mutation sites,family genetic history,medication history of deafness progenitor in each family,Sanger sequencing primers were designed to detect 91 family members in 23 families and provide genetic counseling and eugenic guidance.Fetal hearing was followed up by telephone after birth to assess the accuracy and effectiveness of prenatal diagnosis and genetic counseling protocol.Results Among 80 children with deafness,21 were found to carry the deafness gene mutations.Prenatal diagnosis of 23 fetuses found:7 cases were wild type,6 cases were single heterozygous mutations,2 cases were double gene heterozygous mutations,2 cases were GJB2 double heterozygous mutations(235delC/79G>A and 235delC/341A>G),5 cases were single gene double heterozygous mutations and 1 case was double gene double heterozygous mutation(GJB2/SLC26A4:35delG/176del16/439).After genetic counseling,5 cases of single gene double heterozygous mutations and 1 case of double gene double heterozygous mutation(GJB2/SLC26A4:35delG/176del16/439)were diagnosed with deafness,all of which were induced.Another 17 fetuses were considered to be able to continue pregnancy,including 7 cases of wild-type fetuses,6 cases of single heterozygous mutations,2 cases of double gene heterozygous mutations,and 2 cases of GJB2 double heterozygous mutations,and they were followed up for 5 years after birth and their hearing remained normal.Conclusion The prenatal diagnosis and genetic counseling protocol can provide detailed guidance information for families at high risk of hearing loss,and can effectively reduce the birth of children at high risk of hearing loss,which has good application value.