Rare Genetic Variants in Human APC Are Implicated in Mesiodens and Isolated Supernumerary Teeth
4
Issued Date
2023-03-01
Resource Type
ISSN
16616596
eISSN
14220067
Scopus ID
2-s2.0-85149836323
Pubmed ID
36901686
Journal Title
International Journal of Molecular Sciences
Volume
24
Issue
5
Rights Holder(s)
SCOPUS
Bibliographic Citation
International Journal of Molecular Sciences Vol.24 No.5 (2023)
Suggested Citation
Panyarat C., Nakornchai S., Chintakanon K., Leelaadisorn N., Intachai W., Olsen B., Tongsima S., Adisornkanj P., Ngamphiw C., Cox T.C., Kantaputra P. Rare Genetic Variants in Human APC Are Implicated in Mesiodens and Isolated Supernumerary Teeth. International Journal of Molecular Sciences Vol.24 No.5 (2023). doi:10.3390/ijms24054255 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/81637
Title
Rare Genetic Variants in Human APC Are Implicated in Mesiodens and Isolated Supernumerary Teeth
Other Contributor(s)
Abstract
The activation of Wnt/β-catenin signalling is a prerequisite for odontogenesis. APC, a member of the AXIN-CK1-GSK3β-APC β-catenin destruction complex, functions to modulate Wnt/β-catenin signalling to establish regular teeth number and positions. APC loss-of-function mutations are associated with the over-activation of WNT/β-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 β-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>C, p.Val1125Ala; c.6127A>G, p.Ile2043Val; and c.8383G>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>G, p.Cys914Gly, and c.5722A>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.