Disruption of Tgfbr2 in odontoblasts leads to aberrant pulp calcification.

Transforming growth factor ß (TGF-ß) signaling has been implicated in dentin formation and repair; however, the molecular mechanisms underlying dentin formation remain unclear. To address the role of TGF-ß signaling in dentin formation, we analyzed odontoblast-specific Tgfbr2 conditional knockout mice. The mutant mice had aberrant teeth with thin dysplastic dentin and pulpal obliteration, similar to teeth from human patients with dentinogenesis imperfecta type II and dentin dysplasia. In mutant, the odontoblasts lost their cellular polarity, and matrix secretion was disrupted after mantle dentin formation. As a consequence, the amount of predentin decreased significantly, and an ectopic fibrous matrix was formed below the odontoblast layer. This matrix gradually calcified and obliterated the pulp chamber with increasing age. Immunohistochemistry revealed decreased expression of alkaline phosphatase in mutant odontoblasts. In mutant dentin, Dsp expression was reduced, but Dmp1 expression increased significantly. Collagen type I, biglycan, and Dsp were expressed in the ectopic matrix. These results suggest that loss of responsiveness to TGF-ß in odontoblasts results in impaired matrix formation and pulpal obliteration. Our study indicates that TGF-ß signaling plays an important role in dentin formation and pulp protection. Furthermore, our findings may provide new insight into possible mechanisms underlying human hereditary dentin disorders and reparative dentin formation.

FAM20A mutations associated with enamel renal syndrome.

We identified two families with an autosomal-recessive disorder manifested by severe enamel hypoplasia, delayed and failed tooth eruption, misshapen teeth, intrapulpal calcifications, and localized gingival hyperplasia. Genetic analyses identified novel FAM20A mutations associated with the disease phenotype in both families. The proband of Family 1 had an altered splice junction in Intron 1 (g.502011G>C; c.405-1G>C) and a missense mutation in Exon 8 (g.65094G>A; c.1207G>A; p.D403N). The missense mutation is notable because D(403) is strictly conserved among FAM20A homologues, and the corresponding defect in FAM20C caused osteosclerotic bone dysplasia and a loss of kinase activity. The proband at age 12 yrs tested negative for nephrocalcinosis. The proband and her affected father in Family 2 were homozygous for a single nucleotide deletion that altered a splice junction in Intron 10 (g.66622del; c.1361+4del). Minigene analyses demonstrated that this alteration precluded normal splicing. Immunohistochemistry (IHC) of mouse maxillary first molars localized FAM20A in secretory-stage ameloblasts, in odontoblasts, and in the eruption pathway. IHC of kidneys localized FAM20A in the renal tubules. We conclude that FAM20A is likely a secretory pathway kinase and that loss-of-function mutations cause pathology where its phosphorylations are necessary for normal development or homeostasis.

Generalized pulp stones: report of a case with 6-year follow-up.

AIM: To present a mildly mentally retarded patient with generalized pulp stone formation and the six-year follow-up and to discuss the differential diagnosis of the case. SUMMARY: Pulp stones were radiographically detected in the pulp chamber of all permanent teeth in a 25-year-old woman with mild mental retardation who presented for endodontic treatment on tooth no 11 (FDI). The patient's medical, dental and family history was noncontributory. The pulp stone in the pulp chamber of tooth no 11 was removed during canal filing, and root canal treatment completed uneventfully. Six years later, the patient was re-evaluated and the pulp stones were unchanged radiographically. The patient's family history, facial phenotype and karyotype as well as the radiographic, laboratory and physical examination were not consistent with any of the known genetic syndromes associated with generalized pulp stones. Molecular analysis for the DSPP gene proved negative. The aetiology of this case remains unknown. KEY POINTS: Generalized pulp stones occur rarely; Such patients should be referred for genetic evaluation because pulp stones are mostly associated with genetic dentine defects; Pulp stones may hinder root canal treatment; Pulp stones may remain unchanged overtime.

Imaging evalution of the gingival fibromatosis and dental abnormalities syndrome.

OBJECTIVE: The purpose of this study was to evaluate the dentomaxillofacial imaging features of one family affected by the gingival fibromatosis (GF) and dental abnormalities (DA) syndrome. METHODS: Conventional radiographs (periapical and panoramic) and cone beam CT (CBCT) were performed in nine members of this family: four were affected by the syndrome and five were not. RESULTS: The four affected members demonstrated mild generalized GF in association with DA, including hypoplastic amelogenesis imperfecta, intrapulpal calcifications, delay on tooth eruption and pericoronal radiolucencies in unerupted teeth. None of these oral changes were identified in the five unaffected members. All nine members presented alterations in the paranasal sinuses and mucosal thickening of the maxillary sinus was the most common finding. CONCLUSION: Family members not affected by the syndrome showed similar alterations in the paranasal sinuses and CBCT was useful to characterize the dentomaxillofacial features of this new syndrome associating GF and DA.

A dentin sialophosphoprotein mutation that partially disrupts a splice acceptor site causes type II dentin dysplasia.

The dentin sialophosphoprotein (DSPP) gene on chromosome 4q21.3 encodes the major noncollagenous protein in tooth dentin. DSPP mutations are the principal cause of dentin dysplasia type II, dentinogenesis imperfecta type II, and dentinogenesis imperfecta type III. We have identified a DSPP splice junction mutation (IVS2-6T>G) in a family with dentin dysplasia type II. The primary dentition is discolored brown with severe attrition. The mildly discolored permanent dentition has thistle-shaped pulp chambers, pulp stones, and eventual pulp obliteration. The mutation is in the sixth nucleotide from the end of intron 2, perfectly segregates with the disease phenotype, and is absent in 200 normal control chromosomes. An in vitro splicing assay shows that pre-mRNA splicing of the mutant allele generates wild-type mRNA and mRNA lacking exon 3 in approximately equal amounts. Skipping exon 3 might interfere with signal peptide cleavage, causing endoplasmic reticulum stress, and also reduce DSPP secretion, leading to haploinsufficiency.

Case reports of a new syndrome associating gingival fibromatosis and dental abnormalities in a consanguineous family.

BACKGROUND: Gingival fibromatosis (GF) is characterized by fibrotic enlargement of the gingiva that can be inherited as an isolated trait (named hereditary gingival fibromatosis) or as a component of a syndrome. This article reports one kindred affected by a syndrome characterized by GF associated with dental abnormalities (DA) including generalized thin hypoplastic amelogenesis imperfecta (AI). METHODS: To characterize the pattern of inheritance and the clinical features, 70 family members were examined. Hematoxylin and eosin staining, immunohistochemistry, and scanning electronic microscopy (SEM) were performed to identify the alterations on gingiva, teeth, and dental follicles. RESULTS: Examination of the family pedigree demonstrated multiple consanguineous first-cousin marriages and an autosomal recessive trait of inheritance. Four members demonstrated mild GF in association with DA, including generalized thin hypoplastic AI, intrapulpal calcifications, delay of tooth eruption, and pericoronal radiolucencies involving unerupted teeth. One of those four patients also had mental retardation (MR). MR as an isolated feature was observed in six members, whereas isolated GF was found in one individual. A combination of gingivectomy and gingivoplasty followed by regular dental procedures were performed in these patients. Histologic examination of the gingival enlargement revealed a dense connective tissue containing myofibroblasts, islands of odontogenic epithelium, and calcified psammomatous deposits, which resembled cementicle-like structures by SEM. Pericoronal lesions also showed calcified psammomatous deposits in association with islands of odontogenic epithelium. Enamel ultrastructure analysis revealed normal surface alternating with irregular and porous areas. CONCLUSION: To the best of our knowledge, these cases represent a new syndrome within the spectrum of those including GF.

Hereditary pattern for dentinal dysplasia type Id: a case report.

Generalized pulpal calcifications arouse suspicion of diseases or conditions of systemic or hereditary origin. This case report describes a 45-year-old patient with generalized pulpal calcifications and bulging of the roots in areas corresponding to the pulp chambers in otherwise normal teeth. Similar findings were present in the patient's daughters and brother. This pattern of pulpal calcifications is consistent with the hereditary condition of dentinal dysplasia type Id.

Pulp stones throughout the dentition of monozygotic twins: a case report.

Pulpal calcifications are relatively common. However, their occurrence in the entire dentition is relatively infrequent. The presence of such calcification arouses suspicion of systemic or hereditary origin. This case report describes twin sisters with pulpal calcifications in their entire dentitions. No systemic cause was detected. The pattern of calcification was partially consistent with the hereditary condition of dentinal dysplasia.

[Incidence and origin of dental pulp stones]. / Pulpakövek elfordulása és keletkezse.

The authors found pulp stones in more teeth of a 12-years-old girl. The present work discusses the concerning literature and it establishes that these stones are traced back to different aetiological factors. Their role in the toothaces without caries and presence impeding at root treatment is also emphasized.

Spectrum of dentin dysplasia in a family: case report and literature review.

The dentin dysplasias (DD), which may be classified as type 1 (DD1) or type 2 (DD2), form a group of rare, inherited dentin abnormalities that are clinically distinct from dentinogenesis imperfecta. Studies of affected families may help to distinguish different types of DD and provide further insight into their etiology and clinical management. This report describes a family that showed characteristic dental features of DD1, including clinically normal crowns in both primary and permanent dentitions, and mobile teeth that may be associated with premature exfoliation. Radiographic features included calcification of the pulp with crescent-shaped, radiolucent pulp remnants, short, tapering, taurodontic roots, and many periapical pathoses that may be cysts or granulomas. A spectrum of dentin dysplasia was noted within the family. Strategies to prevent pulp and periapical infections and early exfoliation of the teeth include meticulous oral hygiene and effective caries-preventive measures.