Screening for MSX1 and PAX9 gene variants among hypodontia patients in the Jordanian population

This study aimed to sequence the PAX9 and MSX1 genes in a group of Jordanian patients diagnosed with non-syndromic hypodontia. The study also examined whether the identified genetic variants in these key odontogenic genes could be used to assess susceptibility to hypodontia. Fifty Jordanian individuals diagnosed with non-syndromic hypodontia were enrolled in this study. Genomic DNA was extracted, and all exons of PAX9 (Exons 1,2, 3, and 4) and MSX1 (Exons 1 and 2) were amplified using PCR. The Sanger sequencing technique was used to detect genetic variants, which were analyzed for their clinical significance and evolutionary conservation. Several previously reported genetic variants were detected. In MSX1, two missense variants, c. 77G>C; p. (Gly26Ala)(rs567549350) and c. 119C>G; p. (Ala40Gly)(rs36059701), and a regulatory variant, c. *6C > T(rs8670), were identified. In PAX9, six genetic variants were found: c. 5-109G>C (rs12883298), c. 5-54A>G (rs1288923), c. 5-41A>G(rs12883049), c. 631+41G>A(rs2236007), c. 717C>T; p. (His239His)(rs12881240) and c. 718G>C; p. (Ala240Pro)(rs4904210). Additionally, the c. *6C > T (rs8670) variant in MSX1 was associated with upper lateral incisor agenesis. The c. -18G>A (rs186861426) variant in MSX1 was evolutionarily conserved across multiple species, suggesting a potential regulatory role in odontogenesis. This study confirmed the presence of several previously reported PAX9 and MSX1 variants among Jordanian individuals with hypodontia. The findings emphasize the importance of genetic screening for hypodontia but suggest that the identified variants are likely benign polymorphisms rather than causative variants. Further studies with larger sample sizes and functional analyses are needed to determine the regulatory impact of non-coding variants and their role in tooth agenesis.