两个非综合征性聋家系突变分析及孕早期产前诊断

Mutation analysis and early pregnancy prenatal diagnosis for two families affected with non-syndromic hearing loss

目的:明确2个非综合征性聋家系的致病基因,为有再生育需求的家庭提供准确的遗传咨询和孕早期产前诊断服务,明确胎儿的基因型,进行早诊断早干预,预防聋儿的出生。方法:选取2个均生育过1个重度感音神经性聋患儿的家庭,采集先证者及其父母的外周血提取DNA,采用遗传性聋检测试剂盒(PCR-反向杂交法)和一代测序技术,明确受检者基因型后,对有再生育需求的家庭,在母亲孕10～12周抽取绒毛检测胎儿基因型并进行出生后随访。结果:2个家庭中,1号家庭先证者为SLC26A4基因IVS7-2A>G/c.2177insCTAT复合杂合突变,父母双方均为SLC26A4基因杂合突变携带者;2号家庭先证者为GJB2基因c.605ins46/c.512insAACG复合杂合突变,父母双方均为GJB2基因杂合突变携带者;产前诊断结果表明,1号家庭胎儿基因型为SLC26A4基因IVS7-2A>G/c.2177insCTAT复合杂合突变,与其先证者基因型一致,随访胎儿未出生。2号家庭胎儿GJB2基因序列未见异常,随访新生儿听力正常。结论:遗传性聋基因检测技术结合产前诊断对有再生育需求的耳聋家庭起到显著的指导作用,尤其是早孕期的产前诊断,能做到早诊断、早发现、早干预,有效降低了耳聋患儿的出生率。

Objective：The aim of this study is to identify the pathogenic genes of two non-syndromic hearing loss families,provide accurate genetic counseling and early pregnancy prenatal diagnosis services for second birth families,which determine the genotype of the fetus,early diagnosis and early intervention to prevent the birth of deaf children.Method：Two families with a severe sensorineural hearing loss were enrolled in this study.Genomic DNA was extracted from the peripheral venous blood of the proband and parents.The mutations of the four hearing loss susceptibility genes were analyzed by the hereditary hearing loss gene detection kit（PCR reverse hybridization）and Sanger sequencing.After confirming the genotype of the subject,the genotype of the fetus was examined for the fetus with 10 to 12 weeks of gestation,and the neonates were diagnosed with prenatal diagnosis.Result：In the two families,the No.1 family proband was the compound heterozygous mutation of SLC26 A4 gene c.IVS7-2 AG/c.2177 insCTAT,and parents were carriers.The prenatal diagnosis showed that the fetal genotype of No.1 family was a compound heterozygous mutation,and the fetus was not born.The No.2 family proband genotype was the compound heterozygous of GJB2 gene c.605 ins46/c.512 insAACG,and the parents were both carriers.The No.2 family,the prenatal diagnosis showed the fetal genotype of No.2 family GJB2 gene sequence was normal,the newborn passed the hearing screening.Conclusion：Genetic testing of hereditary hearing loss combined with prenatal diagnosis plays a significant role in guiding deaf children with re-fertility needs,especially prenatal diagnosis in early pregnancy,which can achieve early diagnosis,early detection and early intervention,effectively reducing The birth rate of children with deafness.