Differential genetic diagnoses of adult post-lingual hearing loss according to the audiogram pattern and novel candidate gene evaluation

John Hoon Rim, Byunghwa Noh, Young Ik Koh, Sun Young Joo, Kyung Seok Oh, Kyumin Kim, Jung Ah Kim, Da Hye Kim, Hye Youn Kim, Jee Eun Yoo, Seung Tae Lee, Jin Woong Bok, Min Goo Lee, Jinsei Jung, Jae Young Choi, Heon Yung Gee

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Ski-slope hearing loss (HL), which refers to increased auditory threshold at high frequencies, is common in adults. However, genetic contributions to this post-lingual HL remain largely unknown. Here, we prospectively investigated deafness-associated and novel candidate genes causing ski-slope HL. We analyzed 192 families with post-lingual HL via gene panel and/or exome sequencing. With an overall molecular diagnostic rate of 35.4% (68/192) in post-lingual HL, ski-slope HL showed a lower diagnostic rate (30.7%) compared with other conditions (40.7%). In patients who showed HL onset before the age of 40, genetic diagnostic probability was significantly lower for ski-slope HL than for other conditions. Further analysis of 51 genetically undiagnosed patients in the ski-slope HL group identified three variants in delta-like ligand 1 (DLL1), a Notch ligand, which presented in vitro gain-of-function effects on Notch downstream signaling. In conclusion, genetic diagnostic rates in post-lingual HL varied according to audiogram patterns with age-of-onset as a confounding factor. DLL1 was identified as a candidate gene causing ski-slope HL.

Original languageEnglish
Pages (from-to)915-927
Number of pages13
JournalHuman Genetics
Issue number3-4
Publication statusPublished - 2022 Apr

Bibliographical note

Funding Information:
We thank all individuals who participated in this study. This study was supported by the Team Science Award (6-2021-0002 and -0003) of Yonsei University College of Medicine and by the Basic Science Research Program of the National Research Foundation of Korea (NRF) (MSIT; 2018R1A5A2025079 and 2021R1A2C2003549 to HYG, and 2019R1A2C1084033 to JJ) and the Ministry of Health and Welfare, Republic of Korea (HI18C0160 to JYC). We also thank Medical Illustration and Design, part of the Medical Research Support Services of Yonsei University College of Medicine, for all artistic support related to this work.

Publisher Copyright:
© 2021, The Author(s).

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)


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