Identification of OPN3 as associated with non-syndromic oligodontia in a Japanese population
| Autor: | Ryo Watanabe, Yumi Inagaki, Makoto J. Tabata, Toshihiro Tanaka, Yuki Nagata, Takuya Ogawa, Keiji Moriyama, Tatsuo Kawamoto |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
In silico Mutation Missense Oligodontia 030105 genetics & heredity Biology 03 medical and health sciences symbols.namesake Mice Japan Exome Sequencing Genetics Missense mutation Animals Humans Genetic Predisposition to Disease Gene Genetics (clinical) Exome sequencing Anodontia Sanger sequencing Rod Opsins Pedigree 030104 developmental biology Phenotype Mutation (genetic algorithm) symbols Immunohistochemistry Sequence Analysis |
| Zdroj: | Journal of human genetics. 66(8) |
| ISSN: | 1435-232X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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