A Novel LRP6 Mutation Highlights the Role of Wnt Signaling in Tooth Agenesis.

Non-syndromic tooth agenesis (TA) is a rare developmental disorder that impairs oral function, systemic health, psychological well-being, and quality of life. The Wnt signaling pathway plays a central role in TA pathogenesis, and emerging evidence implicates that the low-density lipoprotein receptor-related protein 6 (LRP6) is involved in autosomal-dominant inheritance of TA. In this study, whole-exome sequencing (WES) of a Chinese family uncovered a novel missense mutation (c.692C>T, p.T231M) in LRP6. Sanger sequencing validated this variant, which was identified as a de novo mutation in the proband. Functional assays using qRT-PCR and immunofluorescent staining demonstrated that this mutation impairs LRP6 protein function and disrupts Wnt signaling. Our findings broaden the mutational spectrum of non-syndromic TA and underscore the critical role of LRP6 in TA.