Genetic Variants in DVL3 are Associated With Root Maldevelopment, Tooth Agenesis, Mesiodens, and Oral Exostoses

Area of Science:

• Genetics
• Developmental Biology
• Oral Biology

Background:

• Dishevelled-3 (DVL3) is crucial for WNT signaling, regulating tooth initiation, root formation, and craniofacial patterning.
• Dysregulation of WNT signaling is implicated in various developmental abnormalities.

Purpose of the Study:

• To investigate dental and craniofacial phenotypes in Thai and Turkish patients with rare or novel DVL3 variants.
• To expand the understanding of DVL3's role in odontogenesis and craniofacial development.

Main Methods:

• Clinical and radiographic evaluation of 11 patients.
• Whole-exome and Sanger sequencing to identify DVL3 variants.
• Phenotypic correlation analysis.

Main Results:

• All patients presented with variable dental anomalies, including root malformations, oral exostoses, and mesiodens.
• A dental-predominant phenotype was observed, distinguishing from broader craniofacial/skeletal features in syndromic Robinow syndrome.
• Suggests a potential genotype-phenotype distinction for DVL3 variants.

Conclusions:

• Rare DVL3 variants can primarily manifest as complex dental anomalies, with or without syndromic features.
• Highlights the critical role of DVL3 in regulating odontogenesis and dentoalveolar development via WNT signaling.
• Emphasizes the need for early genetic evaluation for accurate diagnosis and management of DVL3-related conditions.