A Homozygous Wnt10a Mutation Causes Tooth Agenesis With Open Bite

Tooth agenesis (TA) is a prevalent inherited oral disorder, which can be classified into syndromic tooth agenesis (STA) and non-syndromic tooth agenesis (NSTA). WNT10A is one of most common causative gene of TA, and its mutations influence the Wnt/β‐catenin signaling pathway, resulting in TA. Here, we report a family with NSTA. Comprehensive clinical evaluations were conducted in this family. The proband is a 6-year-old boy, with 12 permanent teeth agenesis, taurodontism in the first permanent molars, infra-occlusion of posterior teeth with open bite, and enamel hypoplasia. The proband showed no features of ectodermal dysplasia. The father exhibited no dental anomalies, whereas his mother showed bilateral dens invaginatus in lateral incisors. Whole-exome sequencing (WES) identified a homozygous pathogenic variant in WNT10A (c.637G>A, p.Gly213Ser) in the proband. Both parents were found to be heterozygous carriers of this variant. The resin composite crown restoration treatment was carried out on all deciduous molars to rehabilitate posterior occlusal function. The missense mutant (p.Gly213Ser) has been reported in both general populations and TA patients. Although the p.Gly213Ser variant has not been found to be definitively associated with taurodontism or enamel hypoplasia, it is predicted to be highly deleterious for preventing the proper disulfied bonds formation and hydrophobic interaction with adjacent residues, thereby destabilizing protein fold and inhibiting the WNT signaling activity. Our study reveals a homozygous variant in WNT10A (p.Gly213Ser) as pathogenic for NATS, which helps to guide early diagnosis and multidisciplinary management.