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Identification of OPN3 as associated with non-syndromic oligodontia in a Japanese population

Journal of Human Genetics volume 66, pages 769–775 (2021)Cite this article

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A Correction to this article was published on 06 December 2021

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Abstract

Tooth agenesis is one of the most frequent congenital abnormalities found in the maxillofacial region. Oligodontia, a severe form of tooth agenesis, occurs as an isolated anomaly or as a syndromic feature. We performed whole exome sequencing analyses to identify causative mutation in a Japanese family with three affected individuals with non-syndromic oligodontia. After variant filtering procedures and validation by Sanger sequencing, we identified one missense mutation (c.668 C > T, p.Gly223Asp) in OPN3 at 1q43, encoding a photosensitive G-protein-coupled receptor (GPCR) expressed in various tissues including brain, liver, and adipose. This mutation was predicted to be pathogenic in silico and was not found in the public databases. We further examined 48 genetically unrelated cases by targeted sequencing of the OPN3 gene region and found one additional missense variant in this gene (c.768 C > T, p.Met256Ile) that was also predicted to be pathogenic. Localization of OPN3 protein by immunohistochemical analysis using mouse embryo revealed its specific expression in the tooth gems from bud to bell stages and their surrounding tissues. These results indicated that OPN3 was involved in non-syndromic oligodontia, which has made an anchoring point for clinical application including DNA diagnostics.

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Acknowledgements

We would like to thank all participants and their families for the involvement in this study. We also thank Ms. Makiko Matsuda, Makoto Sugiura, and Momoko Sakaguchi for their kind support and advice to the study. This work was supported in part by JSPS KAKENHI Grant Number 19K10376. The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. A supplemental materials to this article is available online.

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Authors and Affiliations

  1. Department of Maxillofacial Orthognathics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan

    Yumi Inagaki, Takuya Ogawa & Keiji Moriyama

  2. Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan

    Yumi Inagaki, Ryo Watanabe & Toshihiro Tanaka

  3. Section of Biostructural Science, Department of Hard Tissue Engineering, Graduate School of Tokyo Medical and Dental University (TMDU), Tokyo, Japan

    Makoto J. Tabata

  4. BioResource Research Center, Tokyo Medical and Dental University (TMDU), Tokyo, Japan

    Yuki Nagata & Toshihiro Tanaka

  5. Division of Orofacial Functions and Orthodontics, Department of Health Improvement, Kyushu Dental University, Fukuoka, Japan

    Tatsuo Kawamoto

Authors
  1. Yumi Inagaki
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  2. Takuya Ogawa
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  3. Makoto J. Tabata
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  7. Keiji Moriyama
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Corresponding authors

Correspondence to Keiji Moriyama or Toshihiro Tanaka.

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Conflict of interest

Toshihiro Tanaka is Editor-in-Chief of Journal of Human Genetics. He was not involved in the peer-review or handling of the manuscript. The authors have no other competing interests to disclose.

Web Resources

The URLs for the data presented here are as follows: 1000 Genome Project, http://1000genome.org. dbSNP, https://www.ncbi.nlm.nih.gov/snp/. Human Genetic Variation Database, http://www.genome.med.kyoto-u.ac.jp. jMorp, https://jmorp.megabank.tohoku.ac.jp. gnomAD (ExAC), https://gnomad.broadinstitute.org. Mutation Taster, http://www.mutationtaster.org. National Heart, Lung, and Blood Institute Exome Sequencing Project, http://evs.gs.washington.edu/EVS. Online Mendelian Inheritance in Man, http://www.omim.org. PolyPhen-2, http://www.genetics.bwh.harvard.edu/pph2. PROVEAN, http://provean.jcvi.org/index.php. RefSeq, http://www.ncbi.nlm.nih.gov/RefSeq. SIFT, http://sift.bii.a-star.edu.sg

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Inagaki, Y., Ogawa, T., Tabata, M.J. et al. Identification of OPN3 as associated with non-syndromic oligodontia in a Japanese population. J Hum Genet 66, 769–775 (2021). https://doi.org/10.1038/s10038-021-00903-3

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