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

Abstract

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.

Keywords: TMPRSS3; hearing loss; mutations; sensorineural hearing loss.

图 1

携带 TMPRSS3 突变的两个家系图(黑色箭头指向先证者)

图 2

两位先证者的听力结果

图 3

3个位于不同区域的突变的遗传和功能分析

图 4

通过STRING网络预测 TMPRSS3 与其他基因之间的相关功能基因