Journal of Molecular Medicine

, Volume 92, Issue 6, pp 651–663 | Cite as

A novel mutation of TMPRSS3 related to milder auditory phenotype in Korean postlingual deafness: a possible future implication for a personalized auditory rehabilitation

  • Juyong Chung
  • Sang Min Park
  • Sun O Chang
  • Taesu Chung
  • Kyoung Yeul Lee
  • Ah Reum Kim
  • Joo Hyun Park
  • Veronica Kim
  • Woong-Yang Park
  • Seung-Ha Oh
  • Dongsup Kim
  • Woo Jin Park
  • Byung Yoon ChoiEmail author
Original Article


Appropriate customized auditory rehabilitation for hearing impaired subjects requires prediction of residual hearing and progression of hearing loss. Mutations in TMPRSS3 encoding a transmembrane serine protease were reported to be associated with two different autosomal recessive nonsyndromic hearing loss (arNSHL) phenotypes, DFNB8 and DFNB10, in terms of residual hearing that may mandate different rehabilitation. We aimed to reveal the genetic contribution of TMPRSS3 mutations among Korean populations and to correlate the clinical phenotype with TMPRSS3 genotypes. Fifty families that segregated arNSHL and have visited our clinic recently for 2 years were recruited for TMPRSS3 screening. Novel TMPRSS3 variants detected in our cohort were modeled using a predicted three-dimensional (3D) structure of the serine protease domain. The prevalence reached up to 11.2 % (3/27) among subjects with either prelingual hearing loss but retaining some degree of language development or with postlingual ski-slope hearing loss. We also found that a p.A306T allele is a founder allele in this population. Based upon the 3D modeling, we were able to correlate significant retention of residual low-frequency hearing and slower progression of its loss to this novel variant p.T248M that was predicted to have milder pathogenicity. A yeast-based protease assay confirmed a mild pathogenic potential of the p.T248M variant and a tight correlation between the protease activity and the residual hearing. Preservation of this low-frequency hearing should be of utmost importance when considering auditory rehabilitation. Our results significantly narrow down the candidate population for TMPRSS3 sequencing for more efficient genetic diagnosis. More importantly, genotype–phenotype correlation of this gene observed in our cohort suggests that TMPRSS3 can be an appropriate candidate for personalized and customized auditory rehabilitation.

Key message

  • The prevalence of TMPRSS3 mutations among Korean postlingual hearing loss is 8.3 %.

  • The p.A306T variant of TMPRSS3 is the common founder allele in Koreans.

  • A novel variant, p.T248M of TMPRSS3, was predicted to have milder pathogenicity.

  • There was a genotype–phenotype correlation of this gene in Koreans.

  • Our data support implication of this gene for personalized rehabilitation.


DFNB8/10 TMPRSS3 mutations Cochlear implantation Ski-slope audiogram 



This study was supported by the Seoul National University Bundang Hospital research fund and SK Telecom (health connect) (06-2013-094 to B.Y. Choi) and also by the Korean Health Technology R&D project, Ministry for Health, Welfare and Family Affairs, Republic of Korea (No. A111377 to B. Y. Choi). The funding bodies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.


The authors declare no conflict of interests related to this study.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Juyong Chung
    • 1
  • Sang Min Park
    • 2
  • Sun O Chang
    • 3
    • 4
  • Taesu Chung
    • 5
  • Kyoung Yeul Lee
    • 5
  • Ah Reum Kim
    • 3
  • Joo Hyun Park
    • 3
  • Veronica Kim
    • 6
  • Woong-Yang Park
    • 7
    • 8
  • Seung-Ha Oh
    • 3
    • 4
  • Dongsup Kim
    • 5
  • Woo Jin Park
    • 2
  • Byung Yoon Choi
    • 4
    • 9
    Email author
  1. 1.Department of OtolaryngologyAjou University School of MedicineSuwonSouth Korea
  2. 2.Department of Life ScienceGwangju Institute of Science and Technology (GIST)GwangjuRepublic of Korea
  3. 3.Department of Otorhinolaryngology—Head and Neck SurgerySeoul National University College of MedicineSeoulSouth Korea
  4. 4.Sensory Organ Research InstituteSeoul National University Medical Research CenterSeoulSouth Korea
  5. 5.Department of Bio and Brain EngineeringKorea Advanced Institute of Science and TechnologyDaejeonSouth Korea
  6. 6.Department of Cell and System BiologyUniversity of TorontoTorontoCanada
  7. 7.Department of Molecular Cell BiologySungkyunkwan University School of MedicineSuwonSouth Korea
  8. 8.Translational Genomics Laboratory, Samsung InstituteSamsung Medical CenterSeoulSouth Korea
  9. 9.Department of Otolaryngology—Head and Neck SurgerySeoul National University Bundang Hospital, Seoul National University College of MedicineSeongnamSouth Korea

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