WNT10A and RUNX2 mutations associated with non-syndromic tooth agenesis.

The goal of this study was to examine the prevalence of WNT10A and RUNX2 mutations and assess their potential impact on the phenotype of non-syndromic tooth agenesis. The study included 30 participants with non-syndromic tooth agenesis, divided into hypodontia (n = 24) and oligodontia forms (n = 6), and 42 unaffected family members. Genomic DNA from buccal epithelial cells was used for polymerase chain reaction amplification of functionally important exons of the WNT10A and RUNX2 genes. Direct sequencing reactions were performed to confirm the presence of mutations. The trend of increasing prevalence of WNT10A mutations and a slight increase in the prevalence of RUNX2 mutations were revealed in tooth agenesis cases compared to unaffected family members. There was a higher prevalence of hypodontia than oligodontia, increased frequency of females over males with missing teeth, and a wide phenotypic variability was observed in individuals and families analyzed. The common missense mutations (p.Phe228Ile, p.Arg113Cys, p.Asp217Asn, and p.Gly165Arg) and c.114-56T>C in the WNT10A gene and in-frame-deletion/insertions (11A, 24Q, 30Q), synonymous variant c.240G>A, and 424-33dupC in the RUNX2 gene were identified. These findings highlight an important role of WNT10A and RUNX2 mutations in the genetic etiology of non-syndromic tooth agenesis.