Hereditary Dentin Defects

Abstract

By the Shields classification, articulated over 30 years ago, inherited dentin defects are divided into 5 types: 3 types of dentinogenesis imperfecta (DGI), and 2 types of dentin dysplasia (DD). DGI type I is osteogenesis imperfecta (OI) with DGI. OI with DGI is caused, in most cases, by mutations in the 2 genes encoding type I collagen. Many genes are required to generate the enzymes that catalyze collagen's diverse post-translational modifications and its assembly into fibers, fibrils, bundles, and networks. Rare inherited diseases of bone are caused by defects in these genes, and some are occasionally found to include DGI as a feature. Appreciation of the complicated genetic etiology of DGI associated with bony defects splintered the DGI type I description into a multitude of more precisely defined entities, all with their own designations. In contrast, DD-II, DGI-II, and DGI-III, each with its own pattern of inherited defects limited to the dentition, have been found to be caused by various defects in DSPP (dentin sialophosphoprotein), a gene encoding the major non-collagenous proteins of dentin. Only DD-I, an exceedingly rare condition featuring short, blunt roots with obliterated pulp chambers, remains untouched by the revolution in genetics, and its etiology is still a mystery. A major surprise in the characterization of genes underlying inherited dentin defects is the apparent lack of roles played by the genes encoding the less-abundant non-collagenous proteins in dentin, such as dentin matrix protein 1 (DMP1), integrin-binding sialoprotein (IBSP), matrix extracellular phosphoglycoprotein (MEPE), and secreted phosphoprotein-1, or osteopontin (SPP1, OPN). This review discusses the development of the dentin extracellular matrix in the context of its evolution, and discusses the phenotypes and clinical classifications of isolated hereditary defects of tooth dentin in the context of recent genetic data respecting their genetic etiologies.

Frameshift mutations in dentin phosphoprotein and dependence of dentin disease phenotype on mutation location

“…DI-II, DI-III, and DD-II have been viewed as a continuum of defects, (1)(2)(3) and accordingly, they have been mapped to the same region in chromosome 4 and associated with defects in the dentin sialophosphoprotein (DSPP) gene. (4,5) DI-I is a dental manifestation of a subgroup of patients with the generalized collagen disease osteogenesis imperfecta.…”

“…(9) Several mutations have been identified in the region coding for DSP in families with inherited dentin diseases, most of which conform to the features of DI-II. (4,5) With few exceptions, these mutations affect sequences at the signal peptide or at exon-intron junctions, suggesting that they exert their effects principally by disturbing the normal RNA splicing and protein export. (10)(11)(12) Only recently, frameshift mutations were described in the sequence coding for DPP, (12)(13)(14)(15) and this delay can be attributed to difficulties in sequencing and cloning the extremely repetitive DPP code.…”

Dentin Sialophosphoprotein (DSPP) and Dentin

“…Rat, bovine, and porcine DPPs have an apparent molecular mass just under 100-kDa 36, 38), while human DPP migrates at about 140-kDa 32) . Based upon length variations among the human DPP genomic sequences in the databases, human DPP is believed to display length polymorphisms 13) , although size variations were not noted in the one study characterizing the human DPP protein 32) .…”

“…DSPP mutations also cause DGI-III and DD-II 5 -12) . No genes besides DSPP have been implicated in the etiologies of isolated (non syndromic) inherited defects of dentin 13) . Thus, recent genetic studies accentuate the importance of DSPP in both normal and pathological dentin biomineralization.…”

Dentinogenesis Imperfecta: A Case Report of Five Patients in the Same Family Group

“…It is originated in the histodifferentiation during odontogenesis process, being a localized form of mesodermal dysplasia characterized by an alteration of the dental proteins (Surendra et al, 2013;Devaraju et al, 2014). DI types II and III are caused by a defect in dentin sialophosphoprotein gene (DSPP) (Kim & Simmer, 2007).…”