高通量测序技术联合瞬态诱发性耳声发射技术在新生儿遗传性聋筛查中的应用价值研究

Study on the application value of high-throughput sequencing combined with transient evoked otoacoustic emission technology in the screening of newborns for genetic deafness

目的探究高通量测序(NGS)技术联合瞬态诱发性耳声发射(TEOAE)技术在新生儿遗传性聋筛查中的应用价值。方法采用整群随机抽样方法,根据纳入、排除标准选取2018年1月至2020年10月承德市中心医院625例新生儿作为研究对象,均于出生后3~7 d内行新生儿遗传性聋筛查,筛查方法采用NGS技术和TEOAE技术,并于出生后1个月、2个月采用TEO-AE技术进行第1、2次复筛,统计NGS技术、TEOAE技术筛查结果,分析NGS技术联合TEOAE技术筛查新生儿遗传性聋的价值。结果本组共纳入625例新生儿,NGS技术筛查结果显示6.08%存在耳聋基因异常,主要为GJB2基因(2.40%)、SLC26A4基因(2.72%)异常,0.80%存在≥2个耳聋基因位点异常;TEOAE技术初筛8.48%的新生儿未通过,第1次、2次复筛未通过率分别为6.40%、5.12%;NGS技术、TEOAE技术筛查新生儿遗传性聋的曲线下面积(AUC)分别为0.920、0.880,二者联合筛查的AUC最大,为0.976,联合筛查的灵敏度、特异度分别为95.65%、99.50%。结论NGS技术、TEOAE技术均为新生儿遗传性聋筛查的有效方法,二者联合能有效提高筛查效能,减少误诊漏诊。

Objective To explore the application value of high-throughput sequencing(NGS)technology combined with transient evoked otoacoustic emission(TEOAE)technology in the screening of neonatal hereditary deafness.Methods Six hundred and twentyfive newborns in Chengde Central Hospital from January 2018 to October 2020 was selected as subjects by a whole-group random sampling method according to the inclusion and exclusion criteria,all of them were screened for neonatal genetic deafness within 3-7 d after birth,and the screening methods were NGS technique and TEOAE technique,and the 1st and 2nd re-screening was performed by TEOAE technique at 1 and 2 months after birth.The results of the NGS and TEOAE screening were calculated and the value of the NGS technique combined with the TEOAE technique in screening newborns for hereditary deafness was analyzed.Results A total of 625 newborns were included in this group.The NGS technology screening results showed that 6.08% had deafness gene abnormalities,mainly GJB2 gene(2.40%),SLC26A4 gene(2.72%)abnormality,0.80% had≥2 deafness loci Abnormal points;8.48% of newborns failed the initial screening of TEOAE technology,and the failure rates of the first and second re-screening were 6.40% and 5.12% respectively;the area under the curve(AUC)of NGS technology and TEOAE technology in screening newborns for hereditary deafness were 0.920 and 0.880,respectively.The combined screening of the two had the largest AUC,which was 0.976.The sensitivity and specificity of the combined screening were 95.65% and 99.50%,respectively.Conclusion NGS technology and TEOAE technology are both effective methods for neonatal hereditary deafness screening.The combination of the two can effectively improve the screening efficiency and reduce misdiagnosis and missed diagnosis.