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Genotype-phenotype correlations
Original research
Rising of LOXHD1 as a signature causative gene of down-sloping hearing loss in people in their teens and 20s
  1. Bong Jik Kim1,2,
  2. Hyoung Won Jeon3,
  3. Woosung Jeon4,
  4. Jin Hee Han3,
  5. Jayoung Oh3,
  6. Nayoung Yi1,2,
  7. Min Young Kim3,
  8. Minah Kim3,
  9. Justin Namju Kim5,
  10. Bo Hye Kim3,
  11. Joon Young Hyon6,
  12. Dongsup Kim4,
  13. Ja-Won Koo3,
  14. Doo-Yi Oh3,
  15. Byung Yoon Choi3,7
  1. 1 Department of Otolaryngology–Head and Neck Surgery, Chungnam National University College of Medicine, Chungnam National University Sejong Hospital, Sejong, South Korea
  2. 2 Brain Research Institute, Chungnam National University College of Medicine, Daejeon, South Korea
  3. 3 Department of Otorhinolaryngology–Head and Neck Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
  4. 4 Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, South Korea
  5. 5 Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, USA
  6. 6 Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
  7. 7 Sensory Organ Research Institute, Seoul National University Medical Research Center, Seoul, South Korea
  1. Correspondence to Professor Byung Yoon Choi, Department of Otorhinolaryngology–Head & Neck Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam, South Korea; choiby2010{at}gmail.com

Abstract

Background Down-sloping sensorineural hearing loss (SNHL) in people in their teens and 20s hampers efficient learning and communication and in-depth social interactions. Nonetheless, its aetiology remains largely unclear, with the exception of some potential causative genes, none of which stands out especially in people in their teens and 20s. Here, we examined the role and genotype–phenotype correlation of lipoxygenase homology domain 1 (LOXHD1) in down-sloping SNHL through a cohort study.

Methods Based on the Seoul National University Bundang Hospital (SNUBH) genetic deafness cohort, in which the patients show varying degrees of deafness and different onset ages (n=1055), we have established the ‘SNUBH Teenager–Young Adult Down-sloping SNHL’ cohort (10–35 years old) (n=47), all of whom underwent exome sequencing. Three-dimensional molecular modelling, minigene splicing assay and short tandem repeat marker genotyping were performed, and medical records were reviewed.

Results LOXHD1 accounted for 33.3% of all genetically diagnosed cases of down-sloping SNHL (n=18) and 12.8% of cases in the whole down-sloping SNHL cohort (n=47) of young adults. We identified a potential common founder allele, as well as an interesting genotype–phenotype correlation. We also showed that transcript 6 is necessary and probably sufficient for normal hearing.

Conclusions LOXHD1 exceeds other genes in its contribution to down-sloping SNHL in young adults, rising as a signature causative gene, and shows a potential but interesting genotype–phenotype correlation.

  • human genetics
  • otolaryngology
  • germ-line mutation
  • founder effect
  • genetic counseling

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information. The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.

https://doi.org/10.1136/jmedgenet-2020-107594

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    Data availability statement

    All data relevant to the study are included in the article or uploaded as supplementary information. The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.

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    Footnotes

    • BJK and HWJ contributed equally.

    • Contributors Conceptualisation: BJK and BYC; data curation: HWJ, JHH and BHK; formal analysis: BJK, HWJ, WJ, JHH, JO, DYO and BYC; funding acquisition:BJK and BYC; investigation: BJK, JYH and DK; methodology: MYK and MK; project administration: JHH and BYC; resources: BJK and BYC; software: JHH; supervision: DK and J-WK; validation: BJK, NY and JNK; visualisation: HWJ, MYK, WJ, JYH and DYO; writing of original draft: BJK, HWJ and BYC; writing of review and editing: BJK and BYC.

    • Funding This study was supported by the Basic Science Research Program through the National Research Foundation of Korea, funded by the Ministry of Education (2018R1A2B2001054 to BYC, 2017R1D1A1B03034401 to DYO and 2018R1D1A1B07046159 to BJK); a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, South Korea (grant number HI17C0952 to BYC); and the research fund of Chungnam National University (BJK). This document was reviewed by professional editors who are native speakers of English (https://www.textcheck.com/).

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.