Background: Tooth agenesis is the most frequently occurring genetic developmental anomaly in clinical dentistry. The MSX1 gene, essential for tooth development, has been associated with non-syndromic tooth agenesis. This study aims to identify novel MSX1 variants associated with this condition and to understand their impact on tooth development. Methods: This study involved the genetic analysis of two children presenting with non-syndromic tooth agenesis. Conservation analysis and 3D structural modeling were conducted to assess the pathogenicity of these variants. Additionally, a review of 108 patients with known MSX1 variants was performed to identify patterns of tooth agenesis. Results: We discovered two novel MSX1 variants, c.823 T>G and c.890 A>G, located in the second exon of the MSX1 gene. The identified MSX1 variants, c.823 T>G and c.890 A>G, were predicted to be pathogenic. Conservation analysis showed that the impacted amino acids are highly conserved across species, and 3D structural analysis indicated potential disruptions to protein function. Among the 108 patients reviewed, a consistent pattern of tooth agenesis was observed, with the most frequently missing teeth being the maxillary second premolars, the mandibular second premolars, and the maxillary first premolars. Conclusions: This research broadens the known range of MSX1 gene variants and deepens our comprehension of the genetic foundations of non-syndromic tooth agenesis. The findings provide valuable insights for genetic counseling and future research into tooth development, emphasizing the importance of MSX1 in dental anomalies.
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