{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:30:13Z","timestamp":1791973813959,"version":"4.4.0"},"reference-count":56,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T00:00:00Z","timestamp":1676937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Genomics Thailand Research Grant of the Health Systems Research Institute (HSRI)","award":["64-123"],"award-info":[{"award-number":["64-123"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The activation of Wnt\/\u03b2-catenin signalling is a prerequisite for odontogenesis. APC, a member of the AXIN-CK1-GSK3\u03b2-APC \u03b2-catenin destruction complex, functions to modulate Wnt\/\u03b2-catenin signalling to establish regular teeth number and positions. APC loss-of-function mutations are associated with the over-activation of WNT\/\u03b2-catenin signalling and subsequent familial adenomatous polyposis (FAP; MIM 175100) with or without multiple supernumerary teeth. The ablation of Apc function in mice also results in the constitutive activation of \u03b2-catenin in embryonic mouse epithelium and causes supernumerary tooth formation. The objective of this study was to investigate if genetic variants in the APC gene were associated with supernumerary tooth phenotypes. We clinically, radiographically, and molecularly investigated 120 Thai patients with mesiodentes or isolated supernumerary teeth. Whole exome and Sanger sequencing identified three extremely rare heterozygous variants (c.3374T&gt;C, p.Val1125Ala; c.6127A&gt;G, p.Ile2043Val; and c.8383G&gt;A, p.Ala2795Thr) in APC in four patients with mesiodentes or a supernumerary premolar. An additional patient with mesiodens was compound as heterozygous for two APC variants (c.2740T&gt;G, p.Cys914Gly, and c.5722A&gt;T, p.Asn1908Tyr). Rare variants in APC in our patients are likely to contribute to isolated supernumerary dental phenotypes including isolated mesiodens and an isolated supernumerary tooth.<\/jats:p>","DOI":"10.3390\/ijms24054255","type":"journal-article","created":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T02:07:44Z","timestamp":1676945264000},"page":"4255","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Rare Genetic Variants in Human APC Are Implicated in Mesiodens and Isolated Supernumerary Teeth"],"prefix":"10.3390","volume":"24","author":[{"given":"Chomchanok","family":"Panyarat","sequence":"first","affiliation":[{"name":"Center of Excellence in Medical Genetics Research, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Division of Pediatric Dentistry, Department of Orthodontics and Pediatric Dentistry, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siriruk","family":"Nakornchai","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, Faculty of Dentistry, Mahidol University, Bangkok 10400, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanoknart","family":"Chintakanon","sequence":"additional","affiliation":[{"name":"Division of Orthodontics, Department of Orthodontics and Pediatric Dentistry, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niramol","family":"Leelaadisorn","sequence":"additional","affiliation":[{"name":"Theera-Niramol Dental Clinic, Roi-et 45000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Worrachet","family":"Intachai","sequence":"additional","affiliation":[{"name":"Center of Excellence in Medical Genetics Research, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bjorn","family":"Olsen","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sissades","family":"Tongsima","sequence":"additional","affiliation":[{"name":"National Biobank of Thailand, National Science and Technology Development Agency (NSTDA), Thailand Science Park, Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ploy","family":"Adisornkanj","sequence":"additional","affiliation":[{"name":"Center of Excellence in Medical Genetics Research, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Division of Pediatric Dentistry, Department of Orthodontics and Pediatric Dentistry, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Dental Department, Sawang Daen Din Crown Prince Hospital, Sakon Nakhon 47110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8581-397X","authenticated-orcid":false,"given":"Chumpol","family":"Ngamphiw","sequence":"additional","affiliation":[{"name":"National Biobank of Thailand, National Science and Technology Development Agency (NSTDA), Thailand Science Park, Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8015-5528","authenticated-orcid":false,"given":"Timothy C.","family":"Cox","sequence":"additional","affiliation":[{"name":"Departments of Oral & Craniofacial Sciences, School of Dentistry, and Pediatrics, School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9841-0881","authenticated-orcid":false,"given":"Piranit","family":"Kantaputra","sequence":"additional","affiliation":[{"name":"Center of Excellence in Medical Genetics Research, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Division of Pediatric Dentistry, Department of Orthodontics and Pediatric Dentistry, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1046\/j.1365-263X.2002.00366.x","article-title":"Supernumerary teeth: Review of the literature and a survey of 152 cases","volume":"12","author":"Rajab","year":"2002","journal-title":"Int. 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