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...

Full description

Bibliographic Details
Main Authors: In Seok Moon, Andrew R. Grant, Varun Sagi, Heidi L. Rehm, Konstantina M. Stankovic
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-11-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2021.780874/full
_version_ 1818419911308869632
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.
first_indexed 2024-12-14T12:46:05Z
format Article
id doaj.art-60d3ab31f1e84ba7ba640aa84a239115
institution Directory Open Access Journal
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
work_keys_str_mv AT inseokmoon tmprss3genevariantswithimplicationsforauditorytreatmentandcounseling
AT inseokmoon tmprss3genevariantswithimplicationsforauditorytreatmentandcounseling
AT andrewrgrant tmprss3genevariantswithimplicationsforauditorytreatmentandcounseling
AT andrewrgrant tmprss3genevariantswithimplicationsforauditorytreatmentandcounseling
AT varunsagi tmprss3genevariantswithimplicationsforauditorytreatmentandcounseling
AT varunsagi tmprss3genevariantswithimplicationsforauditorytreatmentandcounseling
AT heidilrehm tmprss3genevariantswithimplicationsforauditorytreatmentandcounseling
AT heidilrehm tmprss3genevariantswithimplicationsforauditorytreatmentandcounseling
AT konstantinamstankovic tmprss3genevariantswithimplicationsforauditorytreatmentandcounseling
AT konstantinamstankovic tmprss3genevariantswithimplicationsforauditorytreatmentandcounseling