AUTHOR=Moon In Seok , Grant Andrew R. , Sagi Varun , Rehm Heidi L. , Stankovic Konstantina M. 

TITLE=TMPRSS3 Gene Variants With Implications for Auditory Treatment and Counseling

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.780874

DOI=10.3389/fgene.2021.780874

ISSN=1664-8021

ABSTRACT=<p><bold>Objective:</bold> To identify and report novel variants in the <italic>TMPRSS3</italic> gene and their clinical manifestations related to hearing loss as well as intervention outcomes. This information will be helpful for genetic counseling and treatment planning for these patients.</p><p><bold>Methods:</bold> Literature review of previously reported <italic>TMPRSS3</italic> variants was conducted. Reported variants and associated clinical information was compiled. Additionally, cohort data from 18 patients, and their families, with a positive result for <italic>TMPRSS3</italic>-associated hearing loss were analyzed. Genetic testing included sequencing and copy number variation (CNV) analysis of <italic>TMPRSS3</italic> and the Laboratory for Molecular Medicine’s OtoGenome-v1, -v2, or -v3 panels. Clinical data regarding patient hearing rehabilitation was interpreted along with their genetic testing results and in the context of previously reported cochlear implant outcomes in individuals with <italic>TMPRSS3</italic> variants.</p><p><bold>Results:</bold> There have been 87 previously reported <italic>TMPRSS3</italic> variants associated with non-syndromic hearing loss in more than 20 ancestral groups worldwide. Here we report occurrences of known variants as well as one novel variant: deletion of Exons 1–5 and 13 identified from our cohort of 18 patients. The hearing impairment in many of these families was consistent with that of previously reported patients with <italic>TMPRSS3</italic> variants (i.e., typical down-sloping audiogram). Four patients from our cohort underwent cochlear implantation.</p><p><bold>Conclusion:</bold> Bi-allelic variants of <italic>TMPRSS3</italic> are associated with down-sloping hearing loss regardless of ancestry. The outcome following cochlear implantation in patients with variants of <italic>TMPRSS3</italic> is excellent. Therefore, cochlear implantation is strongly recommended for hearing rehabilitation in these patients.</p>