Dentin dysplasia type I: a challenge for treatment with dental implants.

Head Face Med. 2007;3:31

Authors: Depprich RA, Ommerborn MA, Handschel JG, Naujoks CD, Meyer U, Kübler NR

ABSTRACT: BACKGROUND: Dentin dysplasia type I is characterized by a defect of dentin development with clinical normal appearance of the permanent teeth but no or only rudimentary root formation. Early loss of all teeth and concomitant underdevelopment of the jaws are challenging for successful treatment with dental implants. METHODS: A combination of sinus lifting and onlay bone augmentation based on treatment planning using stereolithographic templates was used in a patient with dentin dysplasia type I to rehabilitate the masticatory function. RESULTS: (i) a predisposition for an increased and accelerated bone resorption was observed in our patient, (ii) bone augmentation was successful using a mixture of allogenic graft material with autogenous bone preventing fast bone resorption, (iii) surgical planning, based on stereolithographic models and surgical templates, facilitated the accurate placement of dental implants. CONCLUSION: Bony augmentation and elaborate treatment planning is helpful for oral rehabilitation of patients with dentin dysplasia type I.

PMID: 17714586 [PubMed - in process]

A novel DSPP mutation is associated with type II dentinogenesis imperfecta in a Chinese family.

BMC Med Genet. 2007;8:52

Authors: Zhang X, Chen L, Liu J, Zhao Z, Qu E, Wang X, Chang W, Xu C, Wang QK, Liu M

BACKGROUND: Hereditary defects of tooth dentin are classified into two main groups: dentin dysplasia (DD) (types I and II) and dentinogenesis imperfecta (DGI) (types I, II, and III). Type II DGI is one of the most common tooth defects with an autosomal dominant mode of inheritance. One disease-causing gene, the dentin sialophosphoprotein (DSPP) gene, has been reported for type II DGI. METHODS: In this study, we characterized a four-generation Chinese family with type II DGI that consists of 18 living family members, including 8 affected individuals. Linkage analysis with polymorphic markers D4S1534 and D4S414 that span the DSPP gene showed that the family is linked to DSPP. All five exons and exon-intron boundaries of DSPP were sequenced in members of type II DGI family. RESULTS: Direct DNA sequence analysis identified a novel mutation (c.49C-->T, p.Pro17Ser) in exon 1 of the DSPP gene. The mutation spot, the Pro17 residue, is the second amino acid of the mature DSP protein, and highly conserved during evolution. The mutation was identified in all affected individuals, but not in normal family members and 100 controls. CONCLUSION: These results suggest that mutation p.Pro17Ser causes type II DGI in the Chinese family. This study identifies a novel mutation in the DSPP gene, and expands the spectrum of mutations that cause DGI.

PMID: 17686168 [PubMed - indexed for MEDLINE]

Phenotypic variation in dentinogenesis imperfecta/dentin dysplasia linked to 4q21.

J Dent Res. 2006 Apr;85(4):329-33

Authors: Beattie ML, Kim JW, Gong SG, Murdoch-Kinch CA, Simmer JP, Hu JC

Dentinogenesis imperfecta (DGI) and dentin dysplasia (DD) are allelic disorders that primarily affect the formation of tooth dentin. Both conditions are autosomal-dominant and can be caused by mutations in the dentin sialophosphoprotein gene (DSPP, 4q21.3). We recruited 23 members of a four-generation kindred, including ten persons with dentin defects, and tested the hypothesis that these defects are linked to DSPP. The primary dentition showed amber discoloration, pulp obliteration, and severe attrition. The secondary dentition showed either pulp obliteration with bulbous crowns and gray discoloration or thistle-tube pulp configurations, normal crowns, and mild gray discoloration. Haplotype analyses showed no recombination between three 4q21-q24 markers and the disease locus. Mutational analyses identified no coding or intron junction sequence variations associated with affection status in DMP1, MEPE, or the DSP portion of DSPP. The defects in the permanent dentition were typically mild and consistent with a diagnosis of DD-II, but some dental features associated with DGI-II were also present. We conclude that DD-II and DGI-II are milder and more severe forms, respectively, of the same disease.

PMID: 16567553 [PubMed - indexed for MEDLINE]

Dentin sialophosphoprotein knockout mouse teeth display widened predentin zone and develop defective dentin mineralization similar to human dentinogenesis imperfecta type III.

J Biol Chem. 2003 Jul 4;278(27):24874-80

Authors: Sreenath T, Thyagarajan T, Hall B, Longenecker G, D'Souza R, Hong S, Wright JT, MacDougall M, Sauk J, Kulkarni AB

Dentin sialophosphoprotein (Dspp) is mainly expressed in teeth by the odontoblasts and preameloblasts. The Dspp mRNA is translated into a single protein, Dspp, and cleaved into two peptides, dentin sialoprotein and dentin phosphoprotein, that are localized within the dentin matrix. Recently, mutations in this gene were identified in human dentinogenesis imperfecta II (Online Mendelian Inheritance in Man (OMIM) accession number 125490) and in dentin dysplasia II (OMIM accession number 125420) syndromes. Herein, we report the generation of Dspp-null mice that develop tooth defects similar to human dentinogenesis imperfecta III with enlarged pulp chambers, increased width of predentin zone, hypomineralization, and pulp exposure. Electron microscopy revealed an irregular mineralization front and a lack of calcospherites coalescence in the dentin. Interestingly, the levels of biglycan and decorin, small leucine-rich proteoglycans, were increased in the widened predentin zone and in void spaces among the calcospherites in the dentin of null teeth. These enhanced levels correlate well with the defective regions in mineralization and further indicate that these molecules may adversely affect the dentin mineralization process by interfering with coalescence of calcospherites. Overall, our results identify a crucial role for Dspp in orchestrating the events essential during dentin mineralization, including potential regulation of proteoglycan levels.

PMID: 12721295 [PubMed - indexed for MEDLINE]

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

Hum Mol Genet. 2002 Oct 1;11(21):2559-65

Authors: Rajpar MH, Koch MJ, Davies RM, Mellody KT, Kielty CM, Dixon MJ

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.

PMID: 12354781 [PubMed - indexed for MEDLINE]

Reduced expression of dentin sialophosphoprotein is associated with dysplastic dentin in mice overexpressing transforming growth factor-beta 1 in teeth.

J Biol Chem. 2001 Apr 6;276(14):11016-20

Authors: Thyagarajan T, Sreenath T, Cho A, Wright JT, Kulkarni AB

Transforming growth factor (TGF)-beta1 is expressed in developing tooth from the initiation stage through adulthood. Odontoblast-specific expression of TGF-beta1 in the tooth continues throughout life; however, the precise biological functions of this growth factor in the odontoblasts are not clearly understood. Herein, we describe the generation of transgenic mice that overexpress active TGF-beta1 predominantly in the odontoblasts. Teeth of these mice show a significant reduction in the tooth mineralization, defective dentin formation, and a relatively high branching of dentinal tubules. Dentin extracellular matrix components such as type I and III collagens are increased and deposited abnormally in the dental pulp, similar to the hereditary human tooth disorders such as dentin dysplasia and dentinogenesis imperfecta. Calcium, one of the crucial inorganic components of mineralization, is also apparently increased in the transgenic mouse teeth. Most importantly, the expression of dentin sialophosphoprotein (dspp), a candidate gene implicated in dentinogenesis imperfecta II (MIM 125420), is significantly down-regulated in the transgenic teeth. Our results provide in vivo evidence suggesting that TGF-beta1 mediated expression of dspp is crucial for dentin mineralization. These findings also provide for the first time a direct experimental evidence indicating that decreased dspp gene expression along with the other cellular changes in odontoblasts may result in human hereditary dental disorders like dentinogenesis imperfecta II (MIM 125420) and dentin dysplasia (MIM 125400 and 125420).

PMID: 11116156 [PubMed - indexed for MEDLINE]

Polarized light study of enamel and dentin dysplasia.

J Dent Res. 1968 May-Jun;47(3):450-6

Authors: Soni NN, Henry JL, Silberkweit M

PMID: 5240796 [PubMed - indexed for MEDLINE]

Fluoride and the calcification of the rat incisor.

J Dent Res. 1966 Sep-Oct;45(5):1567

Authors: Toda Y, Van Huysen G

PMID: 5225336 [PubMed - indexed for MEDLINE]

Abscopal and direct effects on calcium mobilization, alkaline phosphatase levels, and dentin formation following x-irradiation of either the rat incisor or the thyroid-parathyroid region.

J Dent Res. 1966 Sep-Oct;45(5):1529-38

Authors: Collett WK, Watson JA, Wald N

PMID: 5225327 [PubMed - indexed for MEDLINE]