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Publications

Case Reports Journal Article Epublish

PubMed: 42930425 DOI: 10.3390/dj14100659

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

Dent J (Basel) 14(10)

Authors: Ludovica Fortuna, Roberto Bertozzi, Valentina Trevisan, Chiara Leoni, Angelo Minucci, Maurizio Genuardi, Gaetano Isola, Cristina Grippaudo, Elisabetta Tabolacci

Affiliations

  • Departmental Unit of Molecular and Genomic Diagnostics, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy. Genomics Core Facility, Gemelli Science and Technology Park (G-STeP), Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.
  • Departmental Unit of Molecular and Genomic Diagnostics, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.
  • Genomics Core Facility, Gemelli Science and Technology Park (G-STeP), Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.
  • Center for Rare Diseases, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.
  • Department of Life Sciences and Public Health, Section of Genomic Medicine, Catholic University of the Sacred Heart, 00168 Rome, Italy.
  • Complex Operational Unit of Medical Genetics, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.
  • Unit of Periodontology, Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95123 Catania, Italy.
  • International Research Center on Periodontal and Systemic Health "PerioHealth", University of Catania, 95123 Catania, Italy.
  • UOC Clinica Odontoiatrica, Dipartimento di Neuroscienze, Organi di Senso e Torace, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.
  • Dipartimento Universitario Testa Collo ed Organi di Senso, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.

Abstract

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.

MeSH

Genes, Tooth, Phenotype, Odontogenesis, Exome Sequencing