Identification of novel candidate genes associated with non-syndromic tooth agenesis in Mongolian families

Abstract

Objectives This study aimed to identify genetic variants associated with non-syndromic tooth agenesis (TA) in nine families from Mongolia using whole-exome sequencing (WES) and bioinformatics analysis. Material and methods The study enrolled 41 participants, including three inherited and six non-inherited families. WES analysis was performed on 14 saliva samples from individuals with non-syndromic TA. The potential candidate genes were identified through variant filtering and segregation analysis. The filtered variants were then analyzed in silico mutation impact analysis. Results WES analysis identified 21 variants associated with TA, and 5 of these variants met all filtering criteria. These variants were located in the exome region of MAST4, ITGA6, PITX2, CACNA1S, and CDON genes. The variant in PITX2 was found in eight participants from inherited and non-inherited families, while the MAST4 variant was identified in 6 participants from inherited families. Conclusions The study identified various genetic variant candidates associated with TA in different family groups, with PITX2 being the most commonly identified. Our findings suggest that MAST4 may also be a novel candidate gene for TA due to its association with the Wnt signaling pathway. Additionally, we found that five candidate genes related to focal adhesion and calcium channel complex were significant and essential in tooth development. Clinical relevance Identifying new pathogenic genes associated with TA can improve our understanding of the molecular mechanisms underlying the disease, leading to better diagnosis, prevention, and treatment. Early detection of TA based on biomarkers can improve dental management and facilitate orthodontic and prosthetic treatment.