Mutation of the signal peptide region of the bicistronic gene DSPP affects translocation to the endoplasmic reticulum and results in defective dentine biomineralization.

[dentin dysplasia]

Dentine dysplasia type II is an autosomal dominant disorder in which mineralization of the dentine of the primary teeth is abnormal . On the basis of the phenotypic overlap between , and shared chromosomal location with , dentinogenesis imperfecta type II , a second disorder of dentine mineralization , it has been proposed that the two conditions are allelic . As recent studies have shown that dentinogenesis imperfecta type II results from mutation of the bicistronic dentine sialophosphoprotein gene (DSPP ), we have tested this hypothesis by sequencing DSPP in a family with a history of dentine dysplasia type II . Our results have shown that a missense change , which causes the substitution of a tyrosine for an aspartic acid in the hydrophobic signal peptide domain of the protein , underlies the phenotype in this family . Biochemical analysis has further demonstrated that this mutation causes a failure of translocation of the encoded proteins into the endoplasmic reticulum , and is therefore likely to lead to a loss of function of both dentine sialoprotein and dentine phosphoprotein .