Phenotypic characteristics of taurodontism and a novel WNT10A variant in non-syndromic oligodontia family

Objective: Variants in wingless-type MMTV integration site family member 10A (WNT10A) have been proposed to be the most common cause of non-syndromic oligodontia (NSO). The goal of the present study was to identify the novel WNT10A variants in Chinese families with NSO.

Design: Clinical data were collected from 39 families with oligodontia admitted to the Hospital of Stomatology Hebei Medical University (China) from 2016 to 2022. Whole-exome sequencing (WES) and Sanger sequencing were performed to identify WNT10A variants in three families with non-syndromic oligodontia. Amino acid conservation analysis and protein conformational analysis were conducted for the WNT10A variant. Genotype-phenotype analysis was performed on the previously reported WNT10A variants related to NSO.

Results: We found a novel heterozygous WNT10A variant c.1127 G>A (p.Cys376Tyr) and two reported heterozygous variants c.460 C>A (p.Leu154Met) and c.511 C>T (p.Arg171Cys). Structural modeling showed that the novel WNT10A variant was located in a highly conserved domain, which led to structural damage of WNT10A protein. In addition, we found that the phenotype of the WNT10A variants affected the maxillary second premolars, followed by the mandibular second premolars, and rarely affected the maxillary central incisor. Herein, it is the first time to report that NSO patients with WNT10A monoallele mutation carry taurodontism phenotype and 6.1% prevalence of taurodontism in WNT10A-related NSO patients.

Conclusions: Our results demonstrated that the novel variant c.1127 G>A (p.Cys376Tyr) of WNT10A causes NSO. The present study expanded the known variation spectrum of WNT10A and provided valuable information for genetic counseling of families.