廊坊市16,440例孕妇常见耳聋基因筛查临床实践研究

Common Deafness Genes Screening among 16,440 Pregnant Women in Langfang,Hebei Province

目的基于河北省孕妇耳聋基因筛查项目,针对廊坊市孕妇进行常见耳聋基因筛查,探讨新模式下的临床实践结果。方法采用高通量测序技术对河北省廊坊市听力正常孕妇进行4个常见耳聋基因20个突变位点筛查,根据检测结果其配偶进行相应基因全序列检测、遗传咨询,夫妻双方为同一基因致病突变携带者则进行产前诊断,并对新生儿进行定期随访。结果共16,440例孕妇自愿进行常见耳聋基因筛查,发现耳聋基因携带者881例,携带率为(5.359%,881/16,440)。其中412例携带GJB2突变(2.506%,412/16,440),366例携带SLC26A4突变(2.226%,366/16,440);388例GJB2或SLC26A4阳性孕妇配偶选择进行相应基因全序列检测,检出32对(8.247%,32/388)夫妇同为GJB2或SLC26A4基因突变携带者;7例“双阳”夫妇家庭(夫妻双方为同一基因致病变异携带者)选择行产前诊断,其中3例胎儿诊断为耳聋高风险者;71例(0.43%,71/16,440)孕妇携带GJB3基因突变;50例(0.304%,50/16,440)孕妇携带线粒体MT-RNR1基因突变,预测后代亦为此突变携带者,为药物敏感性个体,需要慎用氨基糖甙类抗生素。阳性孕妇随访发现2例未行产前诊断的双阳夫妇子代出生后未通过听力筛查,并诊断为先天性重度听力损失。结论对孕期女性常见耳聋基因筛查,将防御关口前移至出生前,同时为降低聋儿出生率提供分子流行病学数据基础。

Objective To report a new model of city-wide deafness gene screening for pregnant women in Langfang as part of the Genetic Screening Program for Hearing Loss in pregnant women in Hebei province(GSPHLHB).Methods NGS sequencing was used to screen 20 variation sites of 4 common deafness genes in pregnant women with normal hearing in Langfang,Hebei Province.Spouses of carriers were advised to complete genetic screening for possible carrier status.The couples were counseled on the test results and followed up after birth their babies.Results Of the16,440 voluntarily participating women,881(5.359%)were found to be carriers involving the GJB2(n=412,2.056%)and SLC26A4(366,2.226%)genes.In 338 of these carriers,their spouses also received screening tests and 32(8.247%)were found to carry the same deafness gene mutations as the carrier.Seven of these couples opted for prenatal diagnostic testing and high risk for deafness was confirmed in 3 fetus.GJB3 gene mutations were detected in 71(0.43%)of these pregnant women.Fifty women were mt-DNA carriers(0.304%).They were advised that their offspring and matrilineal family members should strictly avoid exposure to aminoglycoside antibiotics to prevent ototoxic hearing damage.Follow-ups on carriers showed 2 newborns(with both parents being GJB2 or SLC26A4 carriers)failing hearing screening and subsequently diagnosed with congenital severe hearing loss.Conclusion The city-wide deafness gene screening during pregnancy is an effective way to decrease deafness at birth.