LRP4 mutations, dental anomalies, and oral exostoses.
Int J Paediatr Dent
; 2023 Nov 27.
Article
in En
| MEDLINE
| ID: mdl-38013205
ABSTRACT
BACKGROUND:
In order to generate a normal set of teeth, fine-tuning of Wnt/ß-catenin signaling is required, in which WNT ligands bind to their inhibitors or WNT inhibitors bind to their co-receptors. Lrp4 regulates the number of teeth and their morphology by modulating Wnt/ß-catenin signaling as a Wnt/ß-catenin activator or inhibitor, depending on its interactions with the partner proteins, such as Sostdc1 and Dkk1.AIM:
To investigate genetic etiologies of dental anomalies involving LRP4 in a Thai cohort of 250 children and adults with dental anomalies.DESIGN:
Oral and radiographic examinations and whole exome sequencing were performed for every patient.RESULTS:
Two novel (p.Leu1356Arg and p.Ala1702Gly) and three recurrent (p.Arg263His, p.Gly1314Ser, and p.Asn1385Ser) rare variants in low-density lipoprotein receptor-related protein 4 (LRP4 MIM 604270) were identified in 11 patients. Oral exostoses were observed in five patients.CONCLUSION:
Antagonism of Bmp signaling by Sostdc1 requires the presence of Lrp4. Mice lacking Lrp4 have been demonstrated to have alteration of Wnt-Bmp-Shh signaling and an abnormal number of incisors. Therefore, the LRP4 mutations found in our patients may disrupt Wnt-Bmp-Shh signaling, thereby resulting in dental anomalies and oral exostoses. Root maldevelopment in the patients suggests an important role of LRP4 in root morphogenesis.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Int J Paediatr Dent
Journal subject:
ODONTOLOGIA
/
PEDIATRIA
Year:
2023
Document type:
Article
Affiliation country:
Tailandia