A missense variant in LAMB3 underlies variable expressivity in familial tooth agenesis and microdontia

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ABSTRACT

Background

Tooth agenesis is a frequent developmental anomaly with both syndromic and non-syndromic presentation. The LAMB3 gene, typically associated to junctional epidermolysis bullosa, has additionally been implicated in isolated dental phenotypes.

Methods

We report a three-generation family with non-syndromic tooth anomalies, including oligodontia, microdontia, and delayed eruption.
Clinical-exome sequencing was performed on the proband and their parents (trio). Variants were filtered based on frequency, inheritance,
and predicted impact. Segregation was confirmed by Sanger sequencing.

Results

A heterozygous missense variant in LAMB3, c.547C>T, p.(Arg- 183Cys), was identified in the affected family members and was absent in the unaffected mother. The variant is rare and affects a conserved residue. In silico tools support its deleterious effect. Notably, the same variant was previously reported in homozygosity in another family with oligodontia. The phenotypic variability in our family underlines autosomal dominant inheritance with variable expressivity.

Conclusion

This report highlights the role of heterozygous LAMB3 c.547C>T variant in non-syndromic tooth anomalies and expands its phenotypic spectrum. LAMB3 should be considered in the genetic evaluation of isolated tooth agenesis, particularly in families with intrafamilial variability.

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