Identification of DSPP novel variants and phenotype analysis in dentinogenesis dysplasia Shields type II patients

Abstract

Objectives: To investigate the genetic causes and characteristics of teeth of dentin dysplasia Shields Type-II(DD-II) in three Chinese families.Materials and Methods: Three Chinese families affected with DD-II were collected. The whole-exome sequencing(WES) and whole-genome sequencing(WGS) were conducted to screen for variations, and sanger sequencing was used to verify mutation sites. The physical and chemical characteristics of the affected teeth including tooth structure, hardness, mineral content and ultrastructure were investigated.Results: A novel frameshift deletion mutation c.1871_1874del(p.Ser624fs) in DSPP was found in family A and family B, while no pathogenic mutation was found in family C. The affected teeth's pulp cavities were obliterated, and the root canals were smaller than normal teeth and irregularly distributed comprising a network. The patients' teeth also had reduced dentin hardness and highly irregular dentinal tubules. The Mg content of the teeth was signi cantly higher than the controls but the Na content was obviously lower than the controls.Conclusions: A novel frameshift deletion mutation c.1871_1874del(p.Ser624fs) in the DPP region of the DSPP gene caused DD-II. The DD-II teeth demonstrated compromised mechanical properties and changed ultrastructure, suggesting an impaired function of DPP. Our ndings expanded the mutational spectrum of DSPP gene and strengthen the understanding of clinical phenotypes related to the frameshift deletion in the DPP region of the DSPP gene.Clinical Relevance: DSPP mutation can cause the characteristics of the affected teeth including tooth structure, hardness, mineral content and ultrastructure.