WNT10A mutations also associated with agenesis of the maxillary permanent canines, a separate entity

Abstract

Agenesis or isolated hypodontia of the maxillary permanent canines is a very rare dental anomaly. We report on nine unrelated Thai patients with this condition. Three of them had one affected parent. Three heterozygous missense mutations (p.Arg171Cys; p.Gly213Ser; and IVS2+1G>A) were identified in WNT10A in six patients. The p.Gly213Cys mutation was found in four patients. One of the patients who had p.Gly213Ser mutation also had peg-shaped (microdontia of the) maxillary lateral incisors with dens invaginatus. The mothers of two patients who carried the same mutation as their affected sons (p.Gly213Ser and p.Arg171Cys) had microdontia of the maxillary permanent lateral incisor. Our study has demonstrated for the first time that agenesis of the maxillary permanent canines is a distinct entity, associated with mutations in WNT10A. Inheritance appears to be autosomal dominant. Agenesis of the maxillary permanent canines may accompany by microdontia of the maxillary permanent lateral incisors and dens invaginatus of the maxillary permanent lateral incisors. Mutations could not be identified in the coding exons of WNT10A in three patients. They might be located outside the coding exons, including the promoter regions. However, it is likely that agenesis of the maxillary permanent canines is a heterogeneous disorder.

WNT10A coding variants and maxillary lateral incisor agenesis with associated dental anomalies

“…Furthermore, in the present study, all WNT10A variants detected in the patients with MLIA were identified in the heterozygous state. Similarly, only monoallelic WNT10A missense variants have been found in a group of patients with agenesis of the maxillary permanent canines, which is a very rare form of hypodontia . These results are consistent with the observation that homozygous or compound heterozygous WNT10A mutations are associated with larger numbers of missing teeth .…”

“…In addition, Kantaputra et al . showed that p.Gly165Arg was present in four of nine patients with agenesis of the maxillary permanent canines but in only one of 100 Thai controls. Therefore, further studies using a larger group of patients with MLIA are needed to determine the role of p.Gly165Arg in the aetiology of this common anomaly.…”

WNT10B mutations associated with isolated dental anomalies

“…Continuous activation of Wnt signaling leads to continuous tooth renewal and supernumerary teeth, whereas inhibition of Wnt signaling causes arrest of tooth development . Aberrant Wnt signaling has been shown to cause a large variety of human developmental disorders ranging from the absence of a single tooth to life‐threatening cancers …”

“…1 Isolated hypodontia has been reported to be associated with heterozygous mutations in WNT10A, MSX1, PAX9, EDA, AXIN2, EDAR, EDARADD, LPR6, TFAP2B, LPR6, NEMO, KRT17, and GREM2. [2][3][4][5][6] WNT10A and WNT10B are paralogs with 62% amino acid sequence identity in humans and are hypothesized to have evolved after an ancestral gene duplication that occurred during the evolution of the jawed vertebrate lineage. 7,8 The expression of these 2 genes in teeth is very similar, beginning from the initiation of formation through the subsequent stages of development.…”

BCOR mutations and unstoppable root growth: a commentary on oculofaciocardiodental syndrome: novel BCOR mutations and expression in dental cells

“…Besides BCOR, WNT10A appears to be the only gene that is known to be involved in the maxillary permanent canines, as mutations in WNT10A have been reported to cause agenesis of the maxillary permanent canines. 15 CONCLUDING REMARKS Unstoppable root growth in patients with OFCD syndrome appears to be caused by a few mechanisms. BCOR mutations causes abnormal activation of AP-2a, a repressive target of BCOR, leading to increased osteo-dentinogenic potential of MSCs.…”