Methods: Genomic DNA was analyzed in 8 families diagnosed as dentin dysplasia type II or dentinogenesis imperfecta type II and 110 individuals in normal Han Chinese population. The full coding sequence of DPP was amplified by PCR and screened for mutations and variations by direct sequencing and TOPO TA-cloning sequencing. Results: 5 frameshift mutations in DPP coding region were identified in the 5 of 8 families. The mutations co-segregated with the disease phenotypes in affected families and were not found in 220 control chromosomes. In normal population, a total of 25 polymorphisms were revealed in DPP coding region, including 14 in-frame indels (insertion/deletion), 6 nonsynonymous and 5 synonymous single nucleotide polymorphisms (SNPs). These variants display extensive linkage disequilibrium and constitute a total of 15 haplotypes in the investigated population. Conclusions: Our data provide the first evidence that DPP mutations can cause hereditary dentin diseases and suggest that in-frame length variations and missense SNPs in DPP have no obvious pathogenetic effects on dentin formation. The findings shed new light on the causes of the inherited dentin diseases and revealed unusual variation patterns of DPP in human population.
(Supported by grants no. 30771186 and no. 30670115 from the National Natural Science Foundation of China and grant no. 2007CB516707 from the National 973 Project of China)