TMPRSS3复合杂合型突变导致迟发性遗传性听力损失  

Late-onset hereditary hearing loss caused by TMPRSS3 compound heterozygous mutations

作　　者：王月莹 梁悦 黄碧雪 岑晓晴 黄露莎 陈垲钿[1] WANG Yueying;LIANG Yue;HUANG Bixue;CEN Xiaoqing;HUANG Lusha;CHEN Kaitian(Otorhinolaryngology Hospital,the First Affiliated Hospital,Sun Yat-sen University,Guangzhou,510080,China,Institute of Otolaryngology,Sun Yat-sen University)

机构地区：[1]中山大学附属第一医院耳鼻咽喉科医院、中山大学耳鼻咽喉科学研究所,广州510080

出　　处：《临床耳鼻咽喉头颈外科杂志》2024年第8期679-686,共8页Journal of Clinical Otorhinolaryngology Head And Neck Surgery

基　　金：广东省基础与应用基础研究基金项目(No:2022A1515220176)。

摘　　要：目的:明确导致两个无相关性的家系发生迟发性听力损失的遗传病因。方法:利用二代测序,结合Sanger测序和生物信息学预测工具对两个家系成员的临床资料进行分析。结果:两个家系的患者均表现为10余岁起的以中高频为主的渐进性听力下降,且均出现言语识别率下降。二代测序提示听力下降与TMPRSS3基因突变有关,并筛选出3个杂合位点的突变,其中c.383T>C是首次报道的突变。生信预测提示本研究发现的5种TMPRSS3基因突变根据指南被归类为“致病性”或“可能致病性”。结论:TMPRSS3基因复合杂合突变可能是导致迟发性遗传性听力损失的原因,应关注携带该致病基因突变患者青少年时期的听力情况。Objective This study aims to identify the genetic etiology underlying late-onset hearing loss in two unrelated Chinese families.Methods Detailed clinical data of recruited participants of two families were collected and analyzed using next-generation sequencing,combined with Sanger sequencing and bioinformatics tools.Results Patients in both families manifested as down-sloping audiograms,mainly with severe mid-to-high frequency hearing loss as well as decreased speech recognition rate,both of which occurred during the second decade.Next-generation sequencing panels succeeded in identifying mutations in gene TMPRSS3,and three heterozygous mutations were screened out,among which c.383T>C was the first reported mutation.In silico functional analysis and molecular modeling defined the five mutations as"pathogenic"or"likely pathogenic"according to official guideline.Conclusion The novel mutation combinations in TMPRSS3 gene segregated with an exclusive auditory phenotype in the two pedigrees.Our results provided new data regarding the characteristic deafness caused by TMPRSS3 mutations during adolescent period when hearing should be closely monitored.

关 键 词：TMPRSS3 听力下降 基因突变 感音神经性聋 

分 类 号：R764.43[医药卫生—耳鼻咽喉科]