Dentinogenesis Imperfecta 1

A number sign (#) is used with this entry because dentinogenesis imperfecta-1 is caused by mutation in the DSPP gene (125485), encoding dentin phosphoprotein and dentin sialoprotein.

Dentinogenesis imperfecta is an entity clearly distinct from osteogenesis imperfecta with opalescent teeth, and affects only the teeth. There is no increased frequency of bone fractures in this disorder. The frequency may be 1 in 6000 to 8000 children (Witkop, 1957). Witkop and Rao (1971) preferred the term opalescent dentin for this condition as an isolated trait, reserving dentinogenesis imperfecta for the trait when it is combined with osteogenesis imperfecta. Large kindreds have been reported (Roberts and Schour, 1939; Johnson et al., 1959; Bixler et al., 1969; Giansanti and Budnick, 1975; Mars et al., 1976). The teeth are blue-gray or amber brown and opalescent. On dental radiographs, the teeth have bulbous crowns, roots that are narrower than normal, and pulp chambers and root canals that are smaller than normal or completely obliterated. The enamel may split readily from the dentin when subjected to occlusal stress. Shokeir (1972) described an ostensible homozygote; however, the degree of severity in this patient is similar to that seen in some individuals, reported elsewhere, who are heterozygous for the disorder. Sauk et al. (1976) noted an increase in glycosaminoglycans in EDTA soluble dentin in the teeth from patients with this disorder as compared to controls, and less glycosaminoglycan in EDTA insoluble residue.

For the linkage of DGI and GC (139200), Ball et al. (1982) found a maximum lod score of 7.9 at a male recombination fraction of 0.05 and a female recombination fraction of 0.24. The sequence is thought to be 4cen-GC-DGI-MN-4qter. Subtyping of GC was valuable in increasing linkage information in a single large kindred described earlier by Mars et al. (1976). Roulston et al. (1985) studied linkage of the Brandywine form of dentinogenesis imperfecta which they called type III, type I being the form with osteogenesis imperfecta and type II the form previously found to be linked to GC. Type III is less severe than type II. It is called Brandywine type because it was studied by Witkop in the triracial population of Brandywine, Maryland. Roulston et al. (1985) found that a localized form of juvenile periodontitis (170650) was cosegregating with DGI in the family. Two recombinant offspring were observed, indicating that the loci are separate (but closely linked). A gene order of 4cen-JP-GC-DGI was proposed. The 2 forms of DGI may be allelic. On the basis of linkage to RFLPs, Murray (1987) concluded that the DGI1 locus is somewhat more distally located, perhaps on 4q13-q21. Crosby et al. (1995) isolated 6 novel short tandem-repeat polymorphisms (STRPs), 5 of which showed significant evidence of linkage to the dentinogenesis imperfecta locus (which they called the type II locus). The most likely location was in the D4S2691/D4S2692 interval of 6.6 cM.

Shields et al. (1973) proposed that the variety of dentinogenesis imperfecta (dentinogenesis imperfecta type III; 125500) described in the Brandywine isolate by Hursey et al. (1956) was distinct from dentinogenesis imperfecta type II, although Witkop (1975) indicated that they may be the same because of a surname common to individuals with both disorders as well as clinical similarities. (Shields type I dentinogenesis imperfecta is the form associated with osteogenesis imperfecta.)

Osteopontin (SPP1; 166490), the principal phosphorylated glycoprotein of bone, is also expressed in dentin. Crosby et al. (1995) demonstrated that a highly informative short tandem repeat (STR) polymorphism at the SPP1 locus showed no recombination with dentinogenesis imperfecta type II. Nevertheless, sequencing of each exon in individuals affected by this disorder failed to reveal any disease-specific mutations of the SPP1 locus.

A deficiency of dentin sialophosphoprotein (DSPP; 125485) had been suggested as a causative factor in dentinogenesis imperfecta (Takagi and Sasaki, 1988). Zhang et al. (2001) studied a Chinese family with dentinogenesis imperfecta Shields type II. Affected members in 3 generations showed discoloration and severe attrition of their teeth, with obliterated pulp chambers. They found a 2-point lod score of 1.68 at theta = 0.00 with a short tandem repeat polymorphism (STRP) located in intron 2 of the DSPP gene. Screening the DSPP gene, they found a C-to-T transition at nucleotide 3658 that created a stop codon in exon 3 (gln45 to ter) in affected members (see 125485.0001).

In affected members of 4 unrelated Chinese families with dentinogenesis imperfecta type II, Song et al. (2008) identified 4 different heterozygous mutations in the DSPP gene (see, e.g., 125485.0009).