Inherited dentin malformations are autosomal dominant disorders of dentin mineralization and are separated into two main categories, dentinogenesis imperfecta (DGI) and dentin dysplasia (DD) (Shields et al., 1973). Mutations in dentin sialophosphoprotein (DSPP) gene are clinically related to dentinogenesis imperfecta (types II and III) and dentin dysplasia (type II) (De La Dure-Molla et al., 2015, Kim and Simmer, 2007). To date, 60 different dentin sialophosphoprotein gene mutations have been reported to cause inherited dentin defects in human. Clinically, it is characterized by amber and opalescent teeth, poorly mineralized dentin, fractured dental enamel and early obliteration of the pulp chamber (Acevedo et al., 2008, Zhang et al., 2001). Dentin dysplasia type II is similar to dentinogenesis imperfecta type II in terms of deciduous dentition. The affected permanent teeth display mild discoloration, radiographically thistle-shaped pulp chambers and pulp stones (Brenneise & Conway, 1999).

Studies have shown that dentin sialophosphoprotein is mainly expressed in odontoblasts and transiently expressed in preameloblasts during tooth development (Chen et al., 2009). The N-terminus of the dentin sialophosphoprotein is cleaved into glycosylated dentin sialoprotein (DSP) and dentin glycoprotein (DGP). The C-terminal region, dentin phosphoprotein (DPP), is aspartic acid and phosphoserine-rich with a unique sequence of serine-serine-asparagine/aspartate (Ser-Ser-Asx) repeats (Song et al., 2008). Dentin phosphoprotein is more abundant and has been suggested to be involved in initiating dentin matrix mineralization (MacDougall et al., 1997, Suzuki et al., 2009). Dentin sialophosphoprotein gene mutations cause inherited dentin defect through a dominant-negative mechanism (Von Marschall et al., 2012). Deletion or point mutations near the signal peptide might affect signal cleavage and interrupt protein folding and secretion, inducing cell pathology and endoplasmic reticulum (ER) stress (Nieminen et al., 2011). The pathological mechanisms might be better described as a gain-of-function or dominant-negative effect (Von Marschall et al., 2012, Nieminen et al., 2011, Shi et al., 2020). However, the molecular genetic etiology and genotype–phenotype correlations remain unclear.

In the current study, we characterized the dental phenotype and the results of a mutational analysis of three Chinese families with clinically identified inherited dentin diseases. All the mutations were in dentin phosphoprotein coding regions, and the differential phenotypes and the characteristics of affected teeth were investigated.