Mutations in LRP5 and BMP4 are associated with mesiodens, tooth agenesis, root malformation, and oral exostoses.

Autor: Kantaputra PN; Center of Excellence in Medical Genetics Research, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand.; Division of Pediatric Dentistry, Department of Orthodontics and Pediatric Dentistry, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand., Guven Y; Department of Pedodontics, Faculty of Dentistry, Istanbul University, Istanbul, Turkey., Tripuwabhrut K; Division of Orthodontics, Department of Orthodontics and Pediatric Dentistry, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand., Adisornkanj P; Center of Excellence in Medical Genetics Research, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand.; Division of Pediatric Dentistry, Department of Orthodontics and Pediatric Dentistry, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand.; Dental Department, Sawang Daen Din Crown Prince Hospital, Sakon Nakhon, Thailand., Hatsadaloi A; Dental Home Clinic, Khon Kaen, Thailand., Kaewgahya M; Center of Excellence in Medical Genetics Research, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand., Olsen B; Department of Developmental Biology, Harvard School of Dental Medicine, Harvard University, Boston, Massachusetts, USA., Ngamphiw C; National Biobank of Thailand, National Science and Technology Development Agency (NSTDA), Pathum Thani, Thailand., Jatooratthawichot P; School of Chemistry, Institute of Science, and Center for Biomolecular Structure, Function and Application, Suranaree University of Technology, Nakhon Ratchasima, Thailand., Tongsima S; National Biobank of Thailand, National Science and Technology Development Agency (NSTDA), Pathum Thani, Thailand., Ketudat Cairns JR; School of Chemistry, Institute of Science, and Center for Biomolecular Structure, Function and Application, Suranaree University of Technology, Nakhon Ratchasima, Thailand.
Jazyk: angličtina
Zdroj: Clinical genetics [Clin Genet] 2022 Oct; Vol. 102 (4), pp. 333-338. Date of Electronic Publication: 2022 Jul 02.
DOI: 10.1111/cge.14183
Abstrakt: WNT/β-catenin and BMP signaling pathways play important roles in the process of tooth development. Dysregulation of WNT/β-catenin and BMP signaling is implicated in a number of human malformations, including dental anomalies. Whole exome and Sanger sequencing identified seven patients with LRP5 mutations (p.Asn1121Asp, p.Asp856Asn, p.Val1433Met, and p.Val1245Met) and six patients with BMP4 mutations (p.Asn150Lys, p.Gly168Arg, p.Arg269Gln, and p.Ala42Glu). All patients were affected with isolated dental anomalies (dental anomalies with no other structural defects), including mesiodens, tooth agenesis, unseparated roots, narrow roots, shortened and tapered roots, and taurodontism. Five patients with LRP5 and one with BMP4 mutations had oral exostoses. Protein models of LRP5 mutations indicate the possible functional effects of the mutations. Here we report for the first time that mutations in LRP5 are associated with dental anomalies. LRP5 appears to be the first gene related to pathogenesis of mesiodens. We also show for the first time that in addition to tooth agenesis, mutations in BMP4 are also implicated in root maldevelopment and torus mandibularis. Sharing of the phenotypes of the patients with LRP5 and BMP4 mutations, which include root maldevelopment, tooth agenesis, and torus mandibularis, implicates cross talks between the WNT/β-catenin and BMP signaling pathways, especially during root development.
(© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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