[Late-onset hereditary hearing loss caused by <i>TMPRSS3</i> compound heterozygous mutations].

<b>Objective:</b>This study aims to identify the genetic etiology underlying late-onset hearing loss in two unrelated Chinese families. <b>Methods:</b>Detailed clinical data of recruited participants of two families were collected and analyzed using next-generation sequencing, combined with Sanger sequencing and bioinformatics tools. <b>Results:</b>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 <i>TMPRSS3</i>, 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. <b>Conclusion:</b>The novel mutation combinations in <i>TMPRSS3</i> gene segregated with an exclusive auditory phenotype in the two pedigrees. Our results provided new data regarding the characteristic deafness caused by <i>TMPRSS3</i> mutations during adolescent period when hearing should be closely monitored.