A Novel Missense mutation resembling DGI-III in a Korean Family

Objectives: To identify mutations in kindreds suffering from dentinogenesis imperfecta (DGI) and to develop genotype-phenotype relationship. Methods: Oligonucleotide primer pairs for polymerase chain reaction (PCR) amplification were designed that could amplify the entire DSPP coding region, along with short segments (~75 bp) from the adjoining introns. Families with DGI were identified and recruited for mutational analyses. High molecular weight genomic DNA was isolated from peripheral whole blood and relevant PCR amplification products were generated and characterized by DNA sequencing. Results: A novel missense mutation was identified in the exon 3 next to the proposed mutational hotspot (c.52G>T) in DSPP gene. The identified mutation was a T to A transversion at coding position 53 (c.53T>A), which resulted in the substitution of Valine with Aspartic acid (p.V18D). The proband is a child with a severely affected primary dentition, resembling DGI type III pattern with wide open pulp chambers. The kindred spans 3 generations and shows an autosomal dominant pattern of inheritance. Conclusions: DGI type III phenotype was shown with a novel DSPP gene missense mutation in a Korean family, which further strengthens the concept that DGI type III is not confined to Brandywine isolate. This study was funded by grant no 03-2005-003 from the SNUDH research fund.