基因芯片和测序技术检测耳聋基因在产前筛查和诊断中的应用

Application of flow-through hybridization gene chip and sequencing in prenatal screening and diagnosis of deafness gene among the pregnant women

目的:开展耳聋基因的产前筛查及诊断,为非综合征性耳聋二级防控提供依据.方法:使用基因芯片导流杂交技术对有意愿的孕妇行GJB2,SLC26A4,mtDNA及GJB3基因共计13个耳聋突变位点的产前检测,对基因突变携带者的配偶及耳聋患者均行上述耳聋相关基因共43个位点测序,若配偶发生突变,则需对胎儿进行产前诊断.结果:381例孕妇中耳聋基因携带率为3.7%,其中GJB2基因杂合突变7例,纯合突变1例;SLC26A4杂合突变4例;mtDNA基因杂合突变1例;GJB3基因杂合突变1例.携带频率最高的突变位点为GJB2基因235 del C.18对行耳聋基因测序的夫妇中,检出GJB2基因c.79G>A纯合突变3例,杂合突变4例;GJB2基因c.109G>A杂合突变4例.经产前诊断,排除耳聋胎儿,确定1例耳聋基因携带者,5例致病性不明基因携带者及1例新发突变者,由临床医生对父母进行了相关遗传咨询.结论:耳聋基因的产前筛查与诊断对避免耳聋胎儿的出生,耳聋基因携带者的用药及听觉防护指导有重要作用.

Objective:To perfonn the prenatal deafness gene screening and diagnosis to provide the evidence to secondary prevention of nonsyndromic hearing loss in Shenzhen area.Methods:The prenatal deafness gene screening detection were perfonn on 13 mutation sites of GJB2,SLC26A4,mtDNA and GJB3 gene with flow—through hybridization gene chip to willing pregnant women,and the sequencing of 43 sites to all carrier and deaf patients were also performed.If both the parents were carriers,then the prenatal diagnosis should be done.Results:3.7%among the total of 381 pregnant women were deaf gene carrier,which contained 7 GJB2 heterozygous mutation,1 GJB2 homozygous mutation,4 SLC26A4 heterozygous mutation,1 mtDNA heterozygous mutation and 1 GJB3 heterozygous mutation.The most common carrier site was GJB2235 del C.Among the 18 pairs of high-risk parents which were examined by sequencing,3 GJB2 c.79G>A homozygous mutation,4 GJB2 c.79G>A heterozygous mutation,4 GJB2 c.109G>A heterozygous mutation were detected.With the help of the prenatal diagnosis,1 deafiiess gene carrier,5 non—specified gene carrier and 1 de novo mutation carrier were found Besides,all their parents were received related genetic counseling.Conclusion:The prenatal deafness gene screening and diagnosis have great meaning for the bom of deaf fetus detection,the counseling and instruction of drug use and hearing protection to deafness gene carrier.