Clinical and Genetic Characterization of a Family with Tooth Agenesis Carrying a Novel LEF1 Variant

Background: Tooth agenesis is one of the most common developmental anomalies of the human dentition and may occur either as an isolated trait or as part of a syndromic condition. Advances in genomic technologies have facilitated the identification of genes involved in odontogenesis, including LEF1 (Lymphoid Enhancer-Binding Factor 1), a key transcription factor in the WNT signaling pathway. Methods: Whole exome sequencing (WES) was performed in a proband with non-syndromic tooth agenesis to investigate the underlying genetic cause. Parental segregation analysis was performed through Sanger sequencing, and in silico prediction tools were used to assess the potential clinical relevance of the identified variant. A review of the current literature on LEF1-associated dental phenotypes was also conducted. Results: WES identified a novel heterozygous LEF1 variant, c.903G>C, p.(Lys301Asn). The variant co-segregated with the phenotype, being detected in the affected father and absent in the unaffected mother. Although the available evidence is currently insufficient to establish pathogenicity, computational predictions and the known biological role of LEF1 in odontogenesis support its potential functional significance. Conclusions: This study reports a novel LEF1 variant identified in a family with familial non-syndromic tooth agenesis and highlights the importance of integrating genomic findings with clinical and segregation data to inform variant interpretation in hereditary dental anomalies. Further functional and independent genetic evidence will be required to establish the clinical significance of this variant.