Genetic Inheritance of Late-Onset, Down-Sloping Hearing Loss and Its Implications for Auditory Rehabilitation

Mee Hyun Song, Jinsei Jung, John Hoon Rim, Hye Ji Choi, Hack June Lee, Byunghwa Noh, Jun Suk Lee, Heon Yung Gee, Jae Young Choi

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


Objectives: Late-onset, down-sloping sensorineural hearing loss has many genetic and nongenetic etiologies, but the proportion of this commonly encountered type of hearing loss attributable to genetic causes is not well known. In this study, the authors performed genetic analysis using next-generation sequencing techniques in patients showing late-onset, down-sloping sensorineural hearing loss with preserved low-frequency hearing, and investigated the clinical implications of the variants identified. Design: From a cohort of patients with hearing loss at a tertiary referral hospital, 18 unrelated probands with down-sloping sensorineural hearing loss of late onset were included in this study. Down-sloping hearing loss was defined as a mean low-frequency threshold at 250 Hz and 500 Hz less than or equal to 40 dB HL and a mean high-frequency threshold at 1, 2, and 4 kHz greater than 40 dB HL. The authors performed whole-exome sequencing and segregation analysis to identify the genetic causes and evaluated the outcomes of auditory rehabilitation in the patients. Results: There were nine simplex and nine multiplex families included, in which the causative variants were found in six of 18 probands, demonstrating a detection rate of 33.3%. Various types of variants, including five novel and three known variants, were detected in the MYH14, MYH9, USH2A, COL11A2, and TMPRSS3 genes. The outcome of cochlear and middle ear implants in patients identified with pathogenic variants was satisfactory. There was no statistically significant difference between pathogenic variant-positive and pathogenic variant-negative groups in terms of onset age, family history of hearing loss, pure-tone threshold, or speech discrimination scores. Conclusions: The proportion of patients with late-onset, down-sloping hearing loss identified with potentially causative variants was unexpectedly high. Identification of the causative variants will offer insights on hearing loss progression and prognosis regarding various modes of auditory rehabilitation, as well as possible concomitant syndromic features.

Original languageEnglish
Pages (from-to)114-124
Number of pages11
JournalEar and Hearing
Issue number1
Publication statusPublished - 2018

Bibliographical note

Funding Information:
This study was provided with bioresources from the National Biobank of Korea, Centers for Disease Control and Prevention, Republic of Korea (4845-301, 4851-302 and -307). This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2015R1A1A1A05001472 to S.M.H., 2017M3A9E8029714 to J.J.S., 2014M3A9D5A01073865 to C.J.Y., 2018R1A5A2025079 to H.Y.G.) M.H.S., J.J., H.Y.G., and J.Y.C. designed the study conception. J.J, J.H.R., H.J.C., and J.S.L. performed the experiment. M.H.S., J.J., H.J.L., and B.N. analyzed and interpreted the data. M.H.S., J.J., H.J.L., B.N., H.Y.G., and J.H.R. wrote the article.

All Science Journal Classification (ASJC) codes

  • Otorhinolaryngology
  • Speech and Hearing

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