Novel Dental Anomaly-associated Mutations in WNT10A Protein Binding Sites.

OBJECTIVE: WNT/ß-catenin signaling is initiated by binding of a WNT protein to a Frizzled (FZD) receptor and a co-receptor, low-density lipoprotein (LDL) receptor-related protein 5 or 6 (LRP5/6). The objective of this study was to find the genetic variants responsible for dental anomalies found in 4 families. METHODS: Clinical and radiographic examination and whole exome sequencing were performed on 5 patients affected with dental anomalies and the mutant proteins modeled. RESULTS: Five patients were heterozygous for the WNT10A variants, including c.877C>T; p.Arg293Cys, c.874A>G; p.Ser292Gly, c.1042C>T; p.Arg348Cys, and c.1039G>T; p.347GluX. The p.Arg293Cys and p.Ser292Gly mutations are located in the WNT10A N-terminal domain region with binding sites for FZD receptor, porcupine, WNTLESS, and extracellular binding proteins, so they are likely to have adverse effects on binding these proteins. The p.Arg348Cys mutation, which is located in the binding site of LRP5/6 co-receptors, is postulated to result in impaired binding to these co-receptors. The nonsense mutation p.347GluX is predicted to result in the truncation of most of the C-terminal domain, which is likely to disrupt the binding of WNT10A to WNTLESS, the membrane protein that binds lipid-acylated WNT proteins to carry them from the endoplasmic reticulum to the cell surface and FZD. CONCLUSIONS: Four novel mutations in WNT10A were identified in patients with isolated tooth agenesis. The mutations in the N-terminal domain and the interface between the N- and C-terminal domains of WNT10A in our patients are likely to disrupt its binding with FZD, LRP5/6, and various other proteins involved in WNT10A processing and transport, impair WNT and SHH signaling, and subsequently result in tooth agenesis, microdontia, and root maldevelopment.

External apical root resorption in maxillary incisors in orthodontic patients: associated factors and radiographic evaluation.

PURPOSE: This study was performed to evaluate the incidence and degree of external apical root resorption of maxillary incisors after orthodontic treatment and to evaluate particular associated factors related to external apical root resorption. MATERIALS AND METHODS: The records and maxillary incisor periapical radiographs of 181 patients were investigated. Crown and root lengths were measured and compared on the pre- and post-treatment periapical radiographs. Crown length was measured from the center of the incisal edge to the midpoint of the cemento-enamel junction (CEJ). Root length was measured from the CEJ midpoint to the root apex. A correction factor for the enlargement difference was used to calculate root resorption. RESULTS: The periapical radiographs of 564 teeth showed that the average root resorption was 1.39±1.27 (8.24±7.22%) and 1.69±1.14 mm (10.16±6.78%) for the maxillary central and lateral incisors, respectively. The results showed that the dilacerated or pointed roots, maxillary premolar extraction cases, and treatment duration were highly significant factors for root resorption (p<0.001). Allergic condition was a significant factor at p<0.01. Age at the start of treatment, large overjet, and history of facial trauma were also factors significantly associated with root resorption (p<0.05). There was no statistically significant difference in root resorption among the factors of gender, overbite, tongue-thrusting habit, types of malocclusion, and types of bracket. CONCLUSION: These results suggested that orthodontic treatment should be carefully performed in pre-treatment extraction patients who have pointed or dilacerated roots and need long treatment duration.