Candidate gene screening for non-syndromic incisive tooth agenesis: preliminary findings

Dental agenesis is the congenital absence of one or more teeth resulting from disturbances during early dental development and is most often associated with genetic variants in odontogenesis-related genes. However, the specific variants associated with permanent incisor agenesis remain unknown. This study was designed as an exploratory pilot case–control genetic association study aimed at identifying the number of polymorphic variants in selected candidate genes potentially related to maxillary and mandibular lateral incisor agenesis. Salivary DNA was collected from eight individuals (both sexes) with non-syndromic agenesis of permanent lateral incisors and matched to eight controls without agenesis. Exome sequencing targeted genes previously implicated in dental agenesis, including MSH homeobox 1 (MSX1), Wnt family member 10A (WNT10A), Paired box 9 (PAX9), axis inhibition protein 2 (AXIN2), ectodysplasin A (EDA), sprouty RTK signaling antagonist 2 (SPRY2), transforming growth factor alpha (TGFA), SPRY4, and SPARC-related modular calcium binding 2 (SMOC2). Individuals with incisor agenesis exhibited 61.5% more variants than the control group. Significant differences in the number of polymorphic variants were observed in AXIN2, EDA, SPRY2, TGFA, SPRY4, and SMOC2 (p = 0.007), as well as in MSX1 (p = 0.023), whereas no significant differences were found for PAX9 (p = 0.078) and WNT10A (p = 0.756). Notably, EDA, SPRY2, and SMOC2 showed the greatest increase in the number of variants in the affected individuals. Overall, a higher number of genetic variants in these genes was observed in individuals with incisor agenesis, which may suggest a potential role for these genes in lateral incisor agenesis; however, these findings require confirmation in larger, well-powered studies and functional validation of the identified variants.

Agenesis; Genes; Genetic variants; Incisors; Polymorphisms

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