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

doi:10.1007/s00439-021-02367-z

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

Department of Pharmacology

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

Abstract

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 language	English
Pages (from-to)	915-927
Number of pages	13
Journal	Human Genetics
Volume	141
Issue number	3-4
DOIs	https://doi.org/10.1007/s00439-021-02367-z
Publication status	Published - 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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10.1007/s00439-021-02367-z

Cite this

Rim, J. H., Noh, B., Koh, Y. I., Joo, S. Y., Oh, K. S., Kim, K., Kim, J. A., Kim, D. H., Kim, H. Y., Yoo, J. E., Lee, S. T., Bok, J. W., Lee, M. G., Jung, J., Choi, J. Y., & Gee, H. Y. (2022). Differential genetic diagnoses of adult post-lingual hearing loss according to the audiogram pattern and novel candidate gene evaluation. Human Genetics, 141(3-4), 915-927. https://doi.org/10.1007/s00439-021-02367-z

@article{8c2d4d2bbf00410c9db767fd9f9a2ce7,

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

abstract = "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.",

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

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: {\textcopyright} 2021, The Author(s).",

year = "2022",

month = apr,

doi = "10.1007/s00439-021-02367-z",

language = "English",

volume = "141",

pages = "915--927",

journal = "Human Genetics",

issn = "0340-6717",

publisher = "Springer Verlag",

number = "3-4",

}

Rim, JH, Noh, B, Koh, YI, Joo, SY, Oh, KS, Kim, K, Kim, JA, Kim, DH, Kim, HY, Yoo, JE, Lee, ST, Bok, JW, Lee, MG, Jung, J, Choi, JY & Gee, HY 2022, 'Differential genetic diagnoses of adult post-lingual hearing loss according to the audiogram pattern and novel candidate gene evaluation', Human Genetics, vol. 141, no. 3-4, pp. 915-927. https://doi.org/10.1007/s00439-021-02367-z

TY - JOUR

T1 - Differential genetic diagnoses of adult post-lingual hearing loss according to the audiogram pattern and novel candidate gene evaluation

AU - Rim, John Hoon

AU - Noh, Byunghwa

AU - Koh, Young Ik

AU - Joo, Sun Young

AU - Oh, Kyung Seok

AU - Kim, Kyumin

AU - Kim, Jung Ah

AU - Kim, Da Hye

AU - Kim, Hye Youn

AU - Yoo, Jee Eun

AU - Lee, Seung Tae

AU - Bok, Jin Woong

AU - Lee, Min Goo

AU - Jung, Jinsei

AU - Choi, Jae Young

AU - Gee, Heon Yung

N1 - 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).

PY - 2022/4

Y1 - 2022/4

N2 - 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.

AB - 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.

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DO - 10.1007/s00439-021-02367-z

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AN - SCOPUS:85114880179

SN - 0340-6717

VL - 141

SP - 915

EP - 927

JO - Human Genetics

JF - Human Genetics

IS - 3-4

ER -

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

Abstract

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