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

This study aims to identify the genetic etiology underlying late-onset hearing loss in two unrelated Chinese families. Detailed clinical data of recruited participants of two families were collected and analyzed using next-generation sequencing, combined with Sanger sequencing and bioinformatics tools. 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 , 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. The novel mutation combinations in gene segregated with an exclusive auditory phenotype in the two pedigrees. Our results provided new data regarding the characteristic