20个遗传性耳聋家庭的产前诊断

Prenatal Diagnosis in 20 Families with Hereditary Deafness

目的采用基因诊断技术为遗传性聋家庭明确病因,对再生育家庭提供产前诊断服务,明确胎儿基因型,同时提供遗传咨询。方法选取20个有再生育要求的耳聋家庭,首先对先证者及其父母进行GJB2基因、SLC26A4基因全编码区、以及线粒体12S rRNA基因m.1494、m.1555位点进行序列分析,并结合短串联重复序列位点(STR)检测对20个家庭的胎儿绒毛膜或羊水样本进行母体污染鉴定,通过Sanger测序法测定胎儿的耳聋相关基因型。对行产前诊断的新生儿进行随访。结果在20个先证者中,10例为GJB2基因双等位基因变异,10例为SLC26A4基因双等位基因变异。先证者的父母均为致病基因变异的携带者。产前诊断结果显示,6例胎儿基因型为阴性,4例胎儿携带了GJB2基因单杂合变异,5例携带了SLC26A4基因单杂合变异,1例同时携带了GJB2基因和SLC26A4基因的单杂合变异。16例胎儿出生后听力随访正常;4例胎儿基因型分别与家庭先证者相同,胎儿均未出生。结论通过产前诊断,明确了遗传性聋家庭再生育时胎儿的基因型。通过基因型预测耳聋再发风险低的16例胎儿出生后均通过新生儿听力筛查,听力学临床表型与胎儿产前诊断检测结果相符。由此可见,耳聋的产前诊断可以有效地降低遗传性聋儿的出生率。

Objective To identify causes of hereditary deafness,provide prenatal diagnosis services for secondbirth families,conform the genotype of the fetus and provide genetic counseling.Method Twenty families with hereditary deafness were included in this study.Genomic DNA was extracted from peripheral venous blood and mutations of four hearing loss susceptibility genes were analyzed by Sanger sequencing.After confirming the genotype of probands and parents,the genotype of the fetus was examined by Sanger sequencing and short tandem repeat sequence site detection of gestation.Result In the twenty families,mutations in probands involved the GJB2 gene(n=10)and the SLC26A4 gene(n=10),and all parents were carriers.Sixteen of the 20 fetuses prenatally tested were born with normal hearing,of whom 6 showed wild-type genotype,4 carried single heterozygous GJB2 mutations,5 carried single heterozygous SLC26A4 mutations,and 1 carried single heterozygous GJB2 and SLC26A4 mutations.Four fetuses showed the same genotypes as probands,whose parents decided to terminate the pregnancy.Conclusion Genetic testing of hereditary and prenatal diagnosis for hearing loss play a significant role in guiding families with deaf children in their subsequent pregnancies,for early diagnosis,early detection and early intervention to effectively reducing the rate of deafness at birth.