Exome sequencing identifies a novel WNT10A pathogenic variant in a family with non-syndromic oligodontia
Clinical Genetics and Therapeutics
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Primary Categories:
- Basic Research
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Secondary Categories:
- Basic Research
Introduction:
Non-syndromic tooth agenesis (NSTA) is characterized by the absence of ≥ 1 permanent teeth, with at least 6 teeth missing in the oligodontia subtype. To date, more than 10 genes have been implicated in NSTA, including WNT10A. The present study describes the detection and characterization of a WNT10A causal variant for oligodontia in a family with autosomal dominant inheritance.
Methods:
Exome and Sanger sequences were used to analyze the family. To localize the mutated amino acid in a 3D model, the AlphaFold protein structure prediction method was applied.
Results:
Exome sequencing of the index case revealed a rare heterozygous novel WNT10A missense variant c.929T>A;p.(Leu310Gln). Sanger sequencing of three additional family members demonstrated that this variant co-segregated with the phenotype. Moreover, in silico analyses supported variant pathogenicity. The AlphaFold protein structure model showed that the mutant amino acid is located on the surface of the WNT10A protein, at a position opposite the Frizzled-8 and Wntless interaction sites.
Conclusion:
Our analyses renders a phenotype in the canonical Wnt/beta-catenin signaling pathway possible.
Non-syndromic tooth agenesis (NSTA) is characterized by the absence of ≥ 1 permanent teeth, with at least 6 teeth missing in the oligodontia subtype. To date, more than 10 genes have been implicated in NSTA, including WNT10A. The present study describes the detection and characterization of a WNT10A causal variant for oligodontia in a family with autosomal dominant inheritance.
Methods:
Exome and Sanger sequences were used to analyze the family. To localize the mutated amino acid in a 3D model, the AlphaFold protein structure prediction method was applied.
Results:
Exome sequencing of the index case revealed a rare heterozygous novel WNT10A missense variant c.929T>A;p.(Leu310Gln). Sanger sequencing of three additional family members demonstrated that this variant co-segregated with the phenotype. Moreover, in silico analyses supported variant pathogenicity. The AlphaFold protein structure model showed that the mutant amino acid is located on the surface of the WNT10A protein, at a position opposite the Frizzled-8 and Wntless interaction sites.
Conclusion:
Our analyses renders a phenotype in the canonical Wnt/beta-catenin signaling pathway possible.