Genetic Variants in KCTD1 Are Associated with Isolated Dental Anomalies

• Published in: International journal of molecular sciences Vol. 25; no. 10; p. 5179
• Main Authors: Ruangchan, Cholaporn, Ngamphiw, Chumpol, Krasaesin, Annop, Intarak, Narin, Tongsima, Sissades, Kaewgahya, Massupa, Kawasaki, Katsushige, Mahawong, Phitsanu, Paripurana, Kullaya, Sookawat, Bussaneeya, Jatooratthawichot, Peeranat, Cox, Timothy C, Ohazama, Atsushi, Ketudat Cairns, James R, Porntaveetus, Thantrira, Kantaputra, Piranit
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 09.05.2024
• Subjects: Adolescent; Adult; Amino acids; beta Catenin - genetics; beta Catenin - metabolism; Child; Co-Repressor Proteins; Dental enamel; Exome Sequencing; Female; Genetic Variation; Genomes; Humans; hypodontia; Male; Morphogenesis; Odontogenesis; oral exostoses; Patients; Pedigree; Polymorphism; Proteins; root anomalies; supernumerary tooth; taurodontism; Teeth; Tooth Abnormalities - genetics; tooth agenesis; Transcription factors; Wnt Signaling Pathway - genetics; supernumerary tooth; tooth agenesis; hypodontia; oral exostoses; root anomalies; taurodontism
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25105179

KCTD1 plays crucial roles in regulating both the SHH and WNT/β-catenin signaling pathways, which are essential for tooth development. The objective of this study was to investigate if genetic variants in might also be associated with isolated dental anomalies. We clinically and radiographically investigated 362 patients affected with isolated dental anomalies. Whole exome sequencing identified two unrelated families with rare (p.Arg241Gln) or novel (p.Pro243Ser) variants in . The variants segregated with the dental anomalies in all nine patients from the two families. Clinical findings of the patients included taurodontism, unseparated roots, long roots, tooth agenesis, a supernumerary tooth, torus palatinus, and torus mandibularis. The role of Kctd1 in root development is supported by our immunohistochemical study showing high expression of Kctd1 in Hertwig epithelial root sheath. The KCTD1 variants in our patients are the first variants found to be located in the C-terminal domain, which might disrupt protein-protein interactions and/or SUMOylation and subsequently result in aberrant WNT-SHH-BMP signaling and isolated dental anomalies. Functional studies on the p.Arg241Gln variant are consistent with an impact on β-catenin levels and canonical WNT signaling. This is the first report of the association of variants and isolated dental anomalies.