A Novel Variant in Dentin Sialophosphoprotein (DSPP) Gene Causes Dentinogenesis Imperfecta Type III: Case Report

Hereditary dentin defects are a group of autosomal dominant disorders characterized by developmental abnormalities in dentin formation and mineralization. They can be categorized into dentin dysplasia and dentinogenesis imperfecta.

In this study, we report a Chinese family with dentinogenesis imperfecta type III (DGI-III). The proband, a 3-year-old girl, and her mother showed extremely rapid attrition and opalescent discoloration in their teeth. Besides, the primary teeth of the proband showed "shell teeth" radiographically, a phenotype characterized by abnormally enlarged pulp cavities and thin dentin, which are specific features of DGI-III. The clinical data was collected and the genomic DNA was extracted from their peripheral blood samples. Whole-exome sequencing and Sanger sequencing were performed to screen for variations. Then we preliminarily evaluated the secretion of the dentin sialophosphoprotein (DSPP) variant of this family and compared this variant with wild-type DSPP via western blot (WB) analysis in vitro.

The results revealed a novel variant (NM_014208: exon2: c.38C>A: p.A13E) in the signal peptide coding region of the DSPP gene in both the proband and her mother, but not in her father, who had normal teeth. The secretion of the variant DSPP protein was not detected in Human embryonic kidney 293E cells via WB analysis.

Taken together, this study describes the clinical features and genetic etiology of a family with DGI-III, expanding the range of variants that cause DGI-III and enriching the phenotypes associated with variants in the signal peptide segment of DSPP. Functional analysis reveals that this variant disrupts DSPP protein secretion.