Unveiling Novel DSPP Variants and Dental Phenotypes in Dentinogenesis Imperfecta

Variants in the dentin sialophosphoprotein (DSPP) gene are known to cause hereditary dentin disorders, including dentinogenesis imperfecta (DGI), which is characterized by abnormal dentin development and structure. However, the full spectrum of clinical manifestations and the impact of specific variants remain to be fully elucidated.

Oral and radiological examinations were conducted on eight patients from two families. Physical characterization of deciduous DGI teeth and matched controls was performed. Exome and Sanger sequencing were employed for variant detection.

All patients exhibited opalescent teeth with bulbous crowns and pulpal obliteration. A copper-beaten skull appearance was detected in one proband, indicating craniosynostosis and necessitating immediate medical intervention. Ultrastructural analyses revealed a dark and red-yellow tone in deciduous DGI teeth. DGI dentin exhibited decreased mineral density, hardness, and elastic modulus, along with disruption of dentinal tubules, the dentinoenamel junction, and mineral contents. Two novel heterozygous frameshift variants in DSPP, c.2317del and c.3555del, were identified in families A and B, respectively, both located in exon 5, expected to alter the repeating sequence pattern of the dentin phosphoprotein (DPP) protein.

This study identifies two novel frameshift variants in the DPP region associated with compromised dentin properties, composition, and ultrastructure. These findings expand the genotype and phenotype spectra of DSPP-DGI, highlighting the crucial role of dentists not only in addressing dental diseases but also in contributing to broader medical interventions.