TEOAE联合NGS技术在新生儿遗传性耳聋筛查中的应用价值研究

Study on the application value of TEOAE combined with NGS in screening newborn hereditary deafness

摘要:

目的：研究耳声发射技术（Transient evoked otoacoustic emissions, TEOAE）联合高通量测序（Next-generation sequencing technology, NGS）技术在新生儿遗传性耳聋筛查中的应用价值。方法：2~5d的新生儿961例分别接受听力TEOAE筛查、NGS技术检测及TEOAE联合NGS技术筛查，其双亲均进行NGS筛查。TEOAE初筛未通过的新生儿42 d进行复查，复筛仍未通过者3个月后进行听力学检测。对 缝隙连接蛋白β（gap junction protein, beta，GJB）2、溶质载体家族26成员4（Solute carrier family 26 members 4，SLC26A4）、线粒体12srRNA 、GJB3耳聋基因进行检测。比较TEOAE联合NGS技术在新生儿遗传性耳聋筛查中未通过率。结果：961例新生儿中，TEOAE技术初筛，未通过率0.42%（4/961）。NGS基因筛查未通过率为3.22%（31/961），其中GJB2基因突变阳性率1.98%（19/961）、SLC26A4基因突变阳性率0.83%（8/961）、GJB3基因突变阳性率0.31%（3/961）、线粒体12srRNA 基因突变阳性率0.10%（1/961）。TEOAE复筛未通过新生儿双亲至少一人携带耳聋基因。TEOAE联合NGS基因检测中有49例新生儿检出基因突变。与单独NGS技术基因检测或TEOAE技术听力筛查检出率相比，NGS联合TEOAE技术听力筛查的检出率明显升高（χ2=39.291、4.206，P均 <0.05）。结论：TEOAE联合NGS技术在新生儿遗传性耳聋的筛查中的筛查效果优于单独使用TEOAE技术或NGS基因检测技术。

Abstract:

Objective: To study the application value of transient evoked otoacoustic emissions (TEOAE) combined with next generation sequencing technology (NGS) in neonatal hereditary deafness screening. Methods: 961 newborns aged 2-5 days were screened by TEOAE, NGS and TEOAE combined with NGS, and their parents were screened by NGS. Newborns who failed TEOAE screening were reexamined on the 42 nd day, and those who failed TEOAE screening were examined for audiology after 3 months. Twenty two loci of four common deafness genes GJB2, SLC26A4, mitochondrial 12SrRNA and GJB3 were detected. Compared the fail rate of TEOAE combined with NGS in neonatal hereditary deafness screening. Results: TEOAE technology failed to pass the initial screening rate of 0.42% (4 / 961) in 961 newborns. The failure rate of NGS gene screening was 3.22% (31 / 961), including GJB2 gene mutation positive rate 1.98% (19 / 961), SLC26A4 gene mutation positive rate 0.83% (8 / 961), GJB3 gene mutation positive rate 0.31% (3 / 961), mitochondrial 12SrRNA gene mutation positive rate 0.10% (1 / 961). The parents of the newborn, TEOAE screening failed, At least one of them carried the deafness gene. In TEOAE combined with NGS gene detection, gene positive was detected in 49 newborns. Compared with the failure rate of single NGS gene test or TEOAE hearing screening, the failure rate of NGS combined with TEOAE hearing screening was significantly higher (χ2=39.291, 4.206，P<0.05). Conclusions: The screening effect of TEOAE combined with NGS technology in the screening of neonatal hereditary deafness is better than that of TEOAE alone or NGS gene detection technology.