TMPRSS3 Gene Variants With Implications for Auditory Treatment and Counseling
Objective: To identify and report novel variants in the TMPRSS3 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.Methods: Literature review of previously...
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Frontiers Media S.A.
2021-11-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.780874/full |
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author | In Seok Moon In Seok Moon Andrew R. Grant Andrew R. Grant Varun Sagi Varun Sagi Heidi L. Rehm Heidi L. Rehm Konstantina M. Stankovic Konstantina M. Stankovic |
author_facet | In Seok Moon In Seok Moon Andrew R. Grant Andrew R. Grant Varun Sagi Varun Sagi Heidi L. Rehm Heidi L. Rehm Konstantina M. Stankovic Konstantina M. Stankovic |
author_sort | In Seok Moon |
collection | DOAJ |
description | Objective: To identify and report novel variants in the TMPRSS3 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.Methods: Literature review of previously reported TMPRSS3 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 TMPRSS3-associated hearing loss were analyzed. Genetic testing included sequencing and copy number variation (CNV) analysis of TMPRSS3 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 TMPRSS3 variants.Results: There have been 87 previously reported TMPRSS3 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 TMPRSS3 variants (i.e., typical down-sloping audiogram). Four patients from our cohort underwent cochlear implantation.Conclusion: Bi-allelic variants of TMPRSS3 are associated with down-sloping hearing loss regardless of ancestry. The outcome following cochlear implantation in patients with variants of TMPRSS3 is excellent. Therefore, cochlear implantation is strongly recommended for hearing rehabilitation in these patients. |
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issn | 1664-8021 |
language | English |
last_indexed | 2024-12-14T12:46:05Z |
publishDate | 2021-11-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Genetics |
spelling | doaj.art-60d3ab31f1e84ba7ba640aa84a2391152022-12-21T23:00:47ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-11-011210.3389/fgene.2021.780874780874TMPRSS3 Gene Variants With Implications for Auditory Treatment and CounselingIn Seok Moon0In Seok Moon1Andrew R. Grant2Andrew R. Grant3Varun Sagi4Varun Sagi5Heidi L. Rehm6Heidi L. Rehm7Konstantina M. Stankovic8Konstantina M. Stankovic9Department of Otolaryngology—Head and Neck Surgery, Massachusetts Eye and Ear and Harvard Medical School, Boston, MA, United StatesDepartment of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, KoreaProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, United StatesNew York Medical College, Valhalla, NY, United StatesDepartment of Otolaryngology—Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, United StatesUniversity of Minnesota Medical School, Minneapolis, MN, United StatesProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, United StatesCenter for Genomic Medicine and Departments of Pathology and Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United StatesDepartment of Otolaryngology—Head and Neck Surgery, Massachusetts Eye and Ear and Harvard Medical School, Boston, MA, United StatesDepartment of Otolaryngology—Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, United StatesObjective: To identify and report novel variants in the TMPRSS3 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.Methods: Literature review of previously reported TMPRSS3 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 TMPRSS3-associated hearing loss were analyzed. Genetic testing included sequencing and copy number variation (CNV) analysis of TMPRSS3 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 TMPRSS3 variants.Results: There have been 87 previously reported TMPRSS3 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 TMPRSS3 variants (i.e., typical down-sloping audiogram). Four patients from our cohort underwent cochlear implantation.Conclusion: Bi-allelic variants of TMPRSS3 are associated with down-sloping hearing loss regardless of ancestry. The outcome following cochlear implantation in patients with variants of TMPRSS3 is excellent. Therefore, cochlear implantation is strongly recommended for hearing rehabilitation in these patients.https://www.frontiersin.org/articles/10.3389/fgene.2021.780874/fullTMPRSS3cochlear implantationsensorineural hearing lossgenetic counselinghereditary hearing loss |
spellingShingle | In Seok Moon In Seok Moon Andrew R. Grant Andrew R. Grant Varun Sagi Varun Sagi Heidi L. Rehm Heidi L. Rehm Konstantina M. Stankovic Konstantina M. Stankovic TMPRSS3 Gene Variants With Implications for Auditory Treatment and Counseling Frontiers in Genetics TMPRSS3 cochlear implantation sensorineural hearing loss genetic counseling hereditary hearing loss |
title | TMPRSS3 Gene Variants With Implications for Auditory Treatment and Counseling |
title_full | TMPRSS3 Gene Variants With Implications for Auditory Treatment and Counseling |
title_fullStr | TMPRSS3 Gene Variants With Implications for Auditory Treatment and Counseling |
title_full_unstemmed | TMPRSS3 Gene Variants With Implications for Auditory Treatment and Counseling |
title_short | TMPRSS3 Gene Variants With Implications for Auditory Treatment and Counseling |
title_sort | tmprss3 gene variants with implications for auditory treatment and counseling |
topic | TMPRSS3 cochlear implantation sensorineural hearing loss genetic counseling hereditary hearing loss |
url | https://www.frontiersin.org/articles/10.3389/fgene.2021.780874/full |
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