DSPP

The DSPP gene provides instructions for making a protein called dentin sialophosphoprotein. Soon after it is produced, this protein is cut into three smaller proteins: dentin sialoprotein, dentin glycoprotein, and dentin phosphoprotein. These proteins are components of dentin, which is a bone-like substance that makes up the protective middle layer of each tooth.

Although the exact function of the three DSPP-derived proteins is unknown, they appear to be essential for normal tooth development. Dentin phosphoprotein and dentin glycoprotein are thought to be involved in the normal hardening of collagen, the most abundant protein in dentin. Specifically, these proteins play a role in the deposition of mineral crystals among collagen fibers (mineralization).

The DSPP gene is also active at low levels in the inner ear, and may play a role in normal hearing.

dentinogenesis imperfecta - caused by mutations in the DSPP gene

Fewer than 10 mutations in the DSPP gene have been identified in people with dentinogenesis imperfecta. These genetic changes are responsible for two forms of this disorder, type II and type III. Most of these mutations change single protein building blocks (amino acids) in dentin sialophosphoprotein.

A mutation in the DSPP gene also causes a condition called dentin dysplasia type II, which involves abnormalities in tooth development similar to dentinogenesis imperfecta. Some researchers believe that this type of dentin dysplasia and dentinogenesis imperfecta types II and III are actually forms of a single disorder. The mutation associated with dentin dysplasia type II changes a single amino acid in dentin sialophosphoprotein. Specifically, this genetic change replaces the amino acid tyrosine with the amino acid aspartic acid at protein position 6 (written as Tyr6Asp or Y6D).

Mutations in the DSPP gene lead to the production of abnormal DSPP-derived proteins or reduce the amount of these proteins in developing teeth. As a result, teeth have abnormally soft dentin. Teeth with defective dentin are discolored, weak, and prone to breakage and decay. Although the DSPP gene is active in the inner ear, it is unclear how DSPP mutations lead to hearing loss in some families with dentinogenesis imperfecta type II.