Phenotype and genotype characterizations with Dentinogenesis Imperfecta II

Objectives: Dentinogenesis Imperfecta (DGI) type II, an inherited disorder affecting dentin, has been linked to mutations in the dentin sialophosphoprotein (DSPP) gene on chromosome 4q21. The gene product is cleaved into two dentin matrix proteins: dentin sialoprotein (DSP) and dentin phosphoprotein (DPP). The aim of this investigation was to study genotypes and phenotypes in a family with special reference to clinical, radiographic, and histopathologic manifestations.
Methods: Physical and oral examinations were performed in this family including affected boy, mother and unaffected people. Extracted genomic DNA from blood was amplified by the polymerase chain reaction (PCR) using specific DSPP primers. The amplified PCR products were purified and directly sequenced. Furthermore, the PCR products were subcloned into TA cloning plasmids. Individual colony was grown and plasmid DNA isolated and sequenced. Potential alterations were compared to human genomic databases.

Results: The affected boy and mother display typical DGI-II phenotypes, showing teeth-yellow/brown color, tooth attrition, enlarged dental pulp chamber and reduced dentin mineral density. Heterozygous mutation of DSPP gene in the boy and mother was detected. We identified a missense mutation (c.204A>T, p.Arg68Trp) in the DSP domains of the gene. No abnormal mutations were observed in healthy members. This mutation is generated a restriction enzyme site, BtscI. This p.R68W DSP variant changes the DSPP RNA secondary structure and DSP protein secondary dimension structure.

Conclusions: These results suggest that mutation p.Arg68Trp causes DGI-II in the Hispanic family.