Mutations in DSPP cause developmental dentin defects

Mutations in the human DSPP gene has been described in families with dentinogenesis imperfecta type II and dentin dysplasia type II (Zhang et al, 2001; Xiao et al, 2001; Malmgren et al, 2004). Developmental defects of dentin where the principal defect resides in the organic matrix have been classified as three types of dentinogenesis imperfecta and two types of dentin dysplasia (Shields et al, 1973). They all rare and dominantly inherited. A third type of dentin dysplasia has been suggested (Lukinmaa et al, 1996).

Dentinogenesis imperfecta type I is a feature of osteogenesis imperfecta. Dentinogenesis imperfecta type II and dentin dysplasia type II are characterized by abnormal coloration and opalescence of teeth as well as obliteration of the pulp chambers and root channels. The teeth may be barrel-like and the roots short and thin. The enamel is vulnerable to shattering and the dentin for attrition the consequence of which may be infection. Usually the deciduous teeth are more affected than the permanent teeth.

Two familial missense mutations (Val18>Phe and Pro17>Thr) were described in the transmembrane domain coding codons of the DSPP gene (Xiao et al, 2001). Dentinogenesis imperfecta type II was associated with progressive sensosineural high-frequency hearing loss in these families. An Ala15>Val missense change was described in a Swedish family with dentinogenesis imperfecta type II (Malmgren et al, 2004). A missense mutation preceding these (Tyr6Asp) were described in a family with dentin dysplasia type II (Rajpar et al, 2002). A nonsense mutation Gln45>Stop (Zhang et al, 2001) and a G>A mutation in the donor splice site of exon 3 (Xiao et al, 2001) were found in families with dentinogenesis imperfecta type II.

The phenotype of DSPP knockout mouse resembles dentinogenesis imperfecta type III which is characterized by lack of dentin mineralization, widened predentin zone and enlargened pulp chambers with high frequency of pulpal exposures. In the DSPP -/- mice (Sreenath et al, 2003) the molar pulp chambers were enlargened and pulp exposures were observed in an age of 2-3 months. The molars had relatively shortened roots. The predentin region was widened and the dentin-predentin border was irregular. In incisors, globular dentin, an indication of abnomral mineralization of dentin, was observed. The expression of collagen type I was not disturbed, but expression of the proteoglycans biglycan and decorin was increased and these proteoglycans were also abnormally abundabnt in predentin.