脉冲噪声所致爆震性听力损失人员中耳聋基因的突变谱研究

Mutations profiles of deafness genes in explosion-induced hearing loss caused by impulse noise

目的基于全外显子组测序(whole exome sequencing,WES)检测在脉冲噪声所致的爆震性听力损失(explosion-induced hearing loss,EIHL)患者中耳聋基因的突变情况。方法采用横断面研究,收集长期暴露于脉冲噪声作业环境的作业人员共105人,对其工作环境进行噪声测试,并对作业人员进行纯音测听,根据听力情况对发生EIHL的作业人员行WES分析。采用生物信息学方法分析WES结果以筛选与耳聋机制相关的基因在EIHL中存在的基因突变情况。结果发生EIHL的作业人员共75人。纯音测听结果显示,EIHL组人员与同样环境下听力正常的作业人员比较,各个频率上的纯音听力均更差(P<0.05)。通过WES基因筛选,在已被标记为耳聋基因的基因中,有29个耳聋基因在EIHL人群中发生罕见有害错义突变,共包含37个有害错义突变位点。其中GJB4发生突变的频率最高,在4名作业人员中发生突变,突变位点为C292T、C370T和G376A。结论GJB4为本研究EIHL人群中突变频率最高的耳聋基因。

Objective To screen the mutations of the deafness-related genes in explosion-induced hearing loss(EIHL)based on whole exome sequencing(WES).Methods A cross-sectional study was conducted on a total of 105 workers who accepted long-term exposure of impulse noise.Noise testing was conducted in their working environment and pure tone audiometry was conducted on the workers.W hole exome sequencing was performed on workers with EIHL based on their audiometric results.The WES results were analyzed by bioinformatics to screen for mutations in genes related to deafness in workers with EIHL.Results There were 75 workers with EIHL.The pure tone audiometry results showed,compared with the workers with normal hearing,the workers with EIHL displayed a worse performance in different frequencies(P<0.05).Through screening of WES,the rare and detrimental missense mutations happened in 29 deafness-related genes among the workers with EIHL,including 37 harmful mi sense mutation sites.GJB4 had the highest frequency in mutation,which occurs in 4 workers,with mutation sites of C292T,C370T,and G376A.Conclusion GJB4 is the deafness-related gene with the highest mutation frequency in the workers with EIHL.