TMPRSS3 Gene Variants With Implications for Auditory Treatment and Counseling

Area of Science:

• Genetics
• Otolaryngology
• Molecular Biology

Background:

• TMPRSS3 gene variants are linked to non-syndromic hearing loss.
• Understanding these variants is crucial for genetic counseling and treatment planning.

Purpose of the Study:

• Identify novel TMPRSS3 variants and their clinical impact on hearing loss.
• Evaluate intervention outcomes, particularly cochlear implantation, for TMPRSS3-related hearing loss.

Main Methods:

• Conducted a literature review of known TMPRSS3 variants.
• Analyzed genetic and clinical data from 18 patients with TMPRSS3-associated hearing loss.
• Performed genetic testing including sequencing and copy number variation (CNV) analysis.

Main Results:

• Identified 87 previously reported TMPRSS3 variants and one novel variant (deletion of Exons 1-5 and 13).
• Observed down-sloping audiogram patterns consistent with previous reports.
• Four patients showed excellent outcomes after cochlear implantation.

Conclusions:

• Bi-allelic TMPRSS3 variants cause down-sloping hearing loss irrespective of ancestry.
• Cochlear implantation is a highly effective rehabilitation strategy for TMPRSS3-related hearing loss.