Tooth ultrastructure of a novel COL1A2 mutation expanding its genotypic and phenotypic spectra.

OBJECTIVES

To investigate tooth ultrastructure and mutation of two patients in a family affected with osteogenesis imperfecta (OI) type IV and dentinogenesis imperfecta (DGI).

METHODS

Mutations were detected by whole exome and Sanger sequencing. The permanent second molar obtained from the proband (DGI1) and the primary first molar from his affected son (DGI2) were studied for their color, roughness, mineral density, hardness, elastic modulus, mineral content, and ultrastructure, compared to the controls.

RESULTS

Two novel missense COL1A2 variants, c.752C > T (p.Ser251Phe) and c.758G > T (p.Gly253Val), were identified in both patients. The c.758G > T was predicted to be the causative mutation. Pulp cavities of DGI1 (permanent teeth) were obliterated while those of DGI2 (primary teeth) were wide. The patients' teeth had darker and redder colors; reduced dentin hardness; decreased, disorganized, and scattered dentinal tubules and collagen fibers; and irregular dentinoenamel junction (DEJ), compared to controls. Lacunae-like structures were present in DGI2.

CONCLUSIONS

We reported the novel causative mutation, c.758G > T (p.Gly253Val), in COL1A2 for OI type IV and DGI. The DGI dentin demonstrated inferior mechanical property and ultrastructure, suggesting severe disturbances of dentin formation. These could contribute to fragility and prone to infection of DGI teeth. This study expands phenotypic and genotypic spectra of COL1A2 mutations.