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

Abstract

Congenital maxillary lateral incisor agenesis (MLIA) is one of the most common subtypes of dental agenesis. Because little is known with regard to the aetiology of this anomaly, the aim of the study was to determine the contribution of nucleotide variants in wingless-type MMTV integration site family, member 10A (WNT10A), msh homeobox 1 (MSX1), and paired box 9 (PAX9) to the risk of MLIA in a Polish population. Coding regions of the selected genes were analysed by direct sequencing in a group of 20 individuals with unilateral and bilateral MLIA, associated or not with other dental anomalies. The frequencies of the identified nucleotide variants were assessed in an additional cohort of patients with isolated dental agenesis (n = 147) and in 178 controls. Mutation screening showed four non-synonymous substitutions located in the highly conserved coding sequence of WNT10A in five (25%) of the 20 patients. Analysis of genotyping results revealed that three of these variants--p.Arg113Cys, p.Phe228Ile, and the newly identified p.Arg171Leu--may represent aetiological mutations underlying MLIA with associated dental anomalies. No mutations that were potentially aetiologic were identified in MSX1 and PAX9. In conclusion, this is the first report implicating coding variants in the WNT10A gene in the aetiology of MLIA. These results will require further confirmation using larger-scale studies.

WNT10A mutation results in severe tooth agenesis in a family of three sisters

“…In a recent study of individuals with an average number of 8.2 missing teeth, 28% had a pathogenic mutation in WNT10A, whilst figures of up to 56% have been demonstrated in cases affected by higher numbers of missing teeth (up to 14.6) . In addition, seemingly less biologically significant missense mutations in WNT10A have been associated with absent maxillary permanent lateral incisors . The mutation identified in this investigation (c.321C>A) has previously been described in association with several different types of syndromic ectodermal dysplasia and non‐syndromic tooth agenesis.…”

Dental and extra‐oral clinical features in 41 patients with WNT10A gene mutations: A multicentric genotype–phenotype study

“…In other clinical studies, WNT10A mutations were also found in the prevalent and mild phenotypes of maxillary lateral incisor agenesis (MLIA). Indeed, a group of Polish patients with lateral incisor hypodontia carried substitution mutations in a highly conserved region of WNT10A gene in 25% of cases …”

WNT10A/β-catenin pathway in tumorigenesis of papillary thyroid carcinoma

“…In previous studies, WNT10A was shown to play an important role in the pathogenesis of idiopathic pulmonary fibrosis (37), agenesis of the maxillary permanent canines and dental agenesis (38,39), hypohidrotic ectodermal dysplasia (40) and keratoconus (41). Specifically, the aberration of WNT10A leads to malformation of ectodermal appendages during development.…”