长沙地区新生儿听力与耳聋基因联合筛查临床研究

A Study on Combined Hearing and Deafness Gene Screening of Newborns in Changsha Area

目的 分析长沙地区新生儿听力与耳聋基因联合筛查结果,探讨常见耳聋易感基因突变位点在长沙地区新生儿中的分布情况,并评估新生儿听力与耳聋基因联合筛查的有效性。方法 对2018年4月至2019年12月纳入长沙市健康民生项目的新生儿进行听力与耳聋基因联合筛查。听力初筛采用自动听性脑干反应(Automated auditory brainstem response, AABR)或耳声发射(Otoa-coustic emissions, OAE)法,耳聋基因筛查采用目标区域捕获测序技术对耳聋常见的4个基因20个变异位点(4基因panel)或22个基因159个变异位点(22基因panel)进行筛查,分析突变人群携带率,耳聋基因结果为检出异常和无异常,检出异常分为阳性、存在风险、不确定。结果 152,676例新生儿中6,975例检出至少携带一个耳聋基因突变,新生儿突变耳聋基因携带率4.57%(6,975/152,676),同时438例(0.29%)的新生儿具有听力筛查无法检出的药物性耳聋风险。此外研究还发现22基因panel可发现更多GJB2或SLC26A4双等位基因突变个体,检出率显著高于4基因Panel。结论 新生儿常规听力筛查联合耳聋基因筛查,有助于提高早期检出率、识别药物性耳聋高风险人群,通过早期发现进行用药指导,减少药物性耳聋的发生,进行一体化的转诊与个体化的警惕性管理。

Objective To report distribution of common deafness susceptibility gene mutation sites in newborns in Changsha,and effectiveness of newborn hearing and genetic screening.Methods Combined hearing and genetic screening was performed on newborns in 47 hospitals of Changsha from April,2018 to December,2019.Hearing screening included automated auditory brainstem responses(AABRs)or otoacoustic emissions(OAEs),and genetic screening targeted 20 common deafness genes mutation sites on 4 genes(4 gene panels)or 159 mutation sites on 22 genes(22 gene panels)using area capture sequencing technology.Genetic screening results were categorized as normal or abnormal,and the latter was further categorized as positive,at risk or inclusive.Results Of the 152,676 newborns screened,6,975(4.57%)were found to carry at least one deafness gene mutation and 438(0.29%)were at risk for ototoxic deafness that was not revealed by hearing screening.The rate of positive detection was significantly higher with the 22 gene panel than with the 4 gene panel,as bi-allelic mutations of the GJB2 or SLC26A4 genes could be detected in more individuals.Conclusion Routine hearing screening combined with genetic screening in newborns may improve the rate of early deafness detection and help identify people at high risk of drug induced deafness,thus reducing its occurrence.