Evaluation of genetic etiologies and phenotypic characteristics in patients with non-syndromic dental agenesis and oligodontia

Objective: The aim of this study is to contribute to the existing body of knowledge by evaluating the genetic etiologies in non-syndromic tooth agenesis cases with an oligodontia phenotype and identifying phenotypic variations associated with relevant genes. Materials and Methods: A total of 13 individuals aged between 5 and 18 years, who met the inclusion criteria, were included in the study. Peripheral blood samples were collected from the participants, and genomic DNA was isolated using the QIAamp® 96 DNA QIAcube® HT DNA isolation kit. To identify variants, next-generation sequencing (NGS) was performed on the relevant regions using primers covering the coding exons of 13 genes included in the Tooth Dysplasia Panel (WNT10A, WNT10B, PAX9, EDA, EDAR, EDARADD, AXIN2, KRT17, LTBP3, MSX1, SMOC2, TSPEAR). Sequencing was carried out using the Ion GeneStudio™ S5 System. The obtained data were analyzed using the Ion Reporter™ software and Franklin™ by Genoox. To confirm the identified variants and to evaluate segregation in family members, Sanger sequencing was performed; the resulting products were analyzed by capillary electrophoresis on the Applied Biosystems™ 3500 Genetic Analyzer. Variant detection and interpretation of sequencing results were carried out using the Mutation Surveyor® software. Results: As a result of next-generation sequencing analysis, variants were detected in the WNT10A gene in 6 individuals, in the PAX9 gene in 1 individual, and in the EDAR gene in 1 individual. No variants were detected in 5 individuals. Additionally, three novel variants were detected: c.376+2T>C in the WNT10A gene, c.218G>A in the PAX9 gene and c.1073T>G in the WNT10A gene. These variants are reported for the first time in the current literature and provide a new contribution to the literature regarding their association with tooth agenesis. The predominance of variants in the WNT10Agene supports that this gene plays an important role in the etiology of non-syndromic oligodontia. Conclusion: The data obtained through next-generation sequencing enabled the detection of both known and novel variants identified for the first time in the literature; thus, allowing for a better understanding of the genetic causes of tooth agenesis and providing new contributions to the literature. Keywords: Tooth agenesis, Gene, Oligodontia, Variant, Next-generation sequencing