A novel DSPP frameshift mutation causing dentin dysplasia type 2 and disease management strategies.

The present study aims to investigate the mutation in a Chinese family with dentin dysplasia type II (DD-II) and to summarize mutation hotspots, clinical manifestations, and disease management strategies. Phenotype analysis, clinical intervention, mutation screening, and cosegregation analysis within the enrolled family were performed. A summary of the reported mutations in the dentin phosphoprotein (DPP) region of dentin sialophosphoprotein (DSPP) was analyzed. Pathogenicity prediction analysis of the physical properties and function of DSPP variants was performed by bioinformatic processing. Clinical management strategies are discussed. A novel pathogenic mutation (c.2035delA) in the DPP region of DSPP was identified, which was cosegregated in the family. The immature permanent teeth of patients with DD-II presented with X-shaped root canal phenotypes. Most of the identified mutations for DD-II were clustered in the DPP region between nucleotides 1686-2134. Points of differential diagnosis, clinical interventions, and management strategies are proposed. This study revealed a novel DSPP frameshift mutation and presented new clinical features of DD-II. The locus involving nucleotides 1686-2134 of DSPP may represent a mutational hotspot for the disease. Appropriate management of DD-II at different stages is important to avoid the development of secondary dental lesions.

Vps4b heterozygous mice do not develop tooth defects that replicate human dentin dysplasia I.

BACKGROUND: Vacuolar protein sorting-associated protein 4B (VPS4B) is a member of the ATP enzyme AAA protein family, and is mainly involved in protein degradation and cell membrane fusion. Recently, a dominant mutation in this gene was identified in human dentin dysplasia type I (DD-I). Herein, we report the generation of Vps4b knockout (Vps4b KO) mice; however, the homozygous Vps4b KO mutation was embryonic lethal at the early stages of embryo development, and we therefore report the results of heterozygous mutant mice. RESULTS: Mice heterozygous for Vps4b did not develop tooth defects replicating human DD-I. Immunohistochemistry showed that gene KO was successful, as there was decreased expression of Vps4b in heterozygous mice; hematoxylin and eosin (H&E) staining also showed that the width of the pre-dentin zone was increased in heterozygous mice, although the arrangement of the odontoblasts was not significantly different from wild-type (WT) mice. However, H&E staining showed no obvious abnormalities in the bones of heterozygous mice. Moreover, stereomicroscopic and X-ray radiography results indicated no abnormal manifestations in teeth or bones. Furthermore, statistical analysis of the volume and density of dentin and enamel, as well as skeletal analysis, including the volume and separation of trabecular bone analyzed by micro-CT, all showed no differences between Vps4b heterozygotes and WT mice. In addition, there also were no significant differences in bone or cartilage mineralization as evaluated by Alcian blue-Alizarin red staining. CONCLUSIONS: The heterozygous Vps4b KO mice do not develop tooth defects that replicate human DD-I and this is likely to be due to differences in tooth development between the two species. Consequently, further studies are needed to determine whether mice are an appropriate animal model for human tooth diseases.

Dentin dysplasia type I-A dental disease with genetic heterogeneity.

Hereditary dentin disorders include dentinogenesis imperfecta (DGI) and dentin dysplasia (DD), which are autosomal dominant diseases characterized by altered dentin structure such as abnormality in dentin mineralization and the absence of root dentin. Shields classified DGI into three subgroups and DD into two subtypes. Although they are all hereditary dentin diseases, they do not share the same causative genes. To date, the pathogenic genes of DGI type I, which is considered a clinical manifestation of syndrome osteogenesis imperfecta, include COL1A1 and COL1A2. Mutations of the DSPP gene, which encodes the dentin sialophosphoprotein, a major non-collagenous protein, are responsible for three isolated dentinal diseases: DGI-II, DGI-III, and DD-II. However, DD-I appears to be special in that researchers have found three pathogenicity genes-VPS4B, SSUH2, and SMOC2-in three affected families from different countries. It is believed that DD-I is a genetically heterogeneous disease and is distinguished from other types of dentin disorders. This review summarizes the DD-I literature in the context of clinical appearances, radiographic characteristics, and functions of its pathogenic genes and aims to serve clinicians in further understanding and diagnosing this disease.

The fine tuning role of microRNA-RNA interaction in odontoblast differentiation and disease.

Dentinogenesis imperfecta and dentin dysplasia are two common types of genetic oral diseases resulted from the aberrant differentiation of odontoblast. Understanding the mechanisms of odontoblast differentiation is crucial for finding the diagnosis candidate genes and treatment targets for such kinds of diseases. Previous work has identified a battery of transcription factors and growth factors regulating odontoblast differentiation; however, the post-transcriptional regulating mechanisms of them are poorly studied. MicroRNAs (miRNA) are a group of non-coding RNAs widely studied in organ development, inflammation, and tumorigenesis because of its inhibitory effects on the target mRNAs. Also, miRNAs along with their binding targets form a complex competing endogenous RNA (ceRNA) network where miRNAs serve as the fine tuning balancers between their targets. Recent reports demonstrated the essential role of the miRNA pathway in dentinogenesis and the regulatory role of several specific miRNAs in the in vitro model of odontoblast differentiation. Herein, we will discuss the general roles of miRNA in diseases, the function of miRNAs during odontoblast differentiation, and finally the potential pathological mechanisms through which miRNAs cause the odontoblast-related diseases.

Histological and Ultrastructure Analysis of Dentin Dysplasia Type I in Primary Teeth: A Case Report.

Dentin dysplasia type I (DD-I) is a rare human dentin disorder that may affect both the primary and permanent dentitions. The teeth present crowns with normal morphology but short or absent roots. Pulp chamber obliteration and early exfoliation of primary teeth are also observed. We describe herein the typical and atypical features of DD-I presented by a 6-year-old patient, the diagnostic rationale and assessment emphasizing the histological and scanning electron microscopic analysis and the therapeutic approach. The DD-I diagnosis in patients in the mixed dentition period is challenging, especially when only some teeth are affected.

[Difficulties in differential diagnosis of dentin dysplasia. Case report]. / A dentin dysplasia differenciáldiagnosztikai nehézségei. Esetismertetés.

In cases of periapical lesions of unknown origin we have to keep in mind the possibility of dentin dysplasia. From the differential diagnostic point of view of differential diagnosis it is important to recognize this disease as it significantly influences the treatment modality. It is an anomaly of unknown etiology that could affect both deciduous and permanent dentition. Dentin dysplasia presentation varies clinically and radiologically. A rare manifestation which affects 1: 100000 patients is spontaneously occurring either as periapical abscess or odontogenic cyst. The affected teeth could become mobile and eventually lost. Dentin dysplasia is a genetic disease which shows autosomal dominant inheritance and characterized by abnormal formation of dentin structure which occurs during tooth development. For this article we have reviewed available literature and PubMed database. Dentin dysplasia increases the risk of early tooth loss and associated with it esthetic and functional disturbances. As a result it can influence the psychological and social status of the patients and affect their quality of life.

Neural crest deletion of Dlx3 leads to major dentin defects through down-regulation of Dspp.

During development, Dlx3 is expressed in ectodermal appendages such as hair and teeth. Thus far, the evidence that Dlx3 plays a crucial role in tooth development comes from reports showing that autosomal dominant mutations in DLX3 result in severe enamel and dentin defects leading to abscesses and infections. However, the normal function of DLX3 in odontogenesis remains unknown. Here, we use a mouse model to demonstrate that the absence of Dlx3 in the neural crest results in major impairment of odontoblast differentiation and dentin production. Mutant mice develop brittle teeth with hypoplastic dentin and molars with an enlarged pulp chamber and underdeveloped roots. Using this mouse model, we found that dentin sialophosphoprotein (Dspp), a major component of the dentin matrix, is strongly down-regulated in odontoblasts lacking Dlx3. Using ChIP-seq, we further demonstrate the direct binding of Dlx3 to the Dspp promoter in vivo. Luciferase reporter assays determined that Dlx3 positively regulates Dspp expression. This establishes a regulatory pathway where the transcription factor Dlx3 is essential in dentin formation by directly regulating a crucial matrix protein.

Orthodontic treatment of a patient with dentin dysplasia type I.

Dentin dysplasia is a genetic disorder of the teeth that affects the dentin and the pulp. Type I is sometimes called "rootless teeth," because of the loss of organization of the root dentin, which often leads to a shortened root length. The purpose of this article was to present a rare clinical case of a girl who was diagnosed with dentin dysplasia type I when she was referred for an orthodontic evaluation. Panoramic and periapical radiographs showed defective root formation and areas with periapical radiolucencies in several teeth. Her Angle Class I malocclusion was successfully treated, providing esthetic and functional results, without clinical symptoms or signs of periodontitis or odontogenic infections.

[Recognition on dentin dysplasia type â ¡].

Dentin dysplasia type Ⅱ (DD-Ⅱ) is a subtype of hereditary dentin disorders. The dentin sialophosphoprotein (DSPP) gene has been revealed to be the causative gene, whose mutations could affect the normal tooth development process. The lesions involve both deciduous and permanent dentition, mainly manifested as tooth discoloration, attrition and even the subsequent malocclusion. If not treated in time, it will significantly affect the physical and psychological health of patients. The disease is difficult to be diagnosed in clinic accurately as its low incidence and hidden manifestations. The present article aims to discuss the clinical and radiographic characteristics, diagnosis, treatment of DD-Ⅱ, in order to improve the overall understanding on DD-Ⅱ for clinicians.

The effect of lathyrism on dentin structure of the rat incisors: a morphometric and scanning electron microscopic investigation.

BACKGROUND: The present study was designed to study the effect of beta-aminopropionitrile (beta-APN), present in Lathyrus sativus grass pea consumed in drought prone areas, on dentin of the continuously erupting rat incisors. METHODS: Eighteen adult male rats were used. In the experimental group (18 rats), lathyrism was induced by a once daily subcutaneous administration of beta-APN for 40 days. The maxillary and mandibular incisors were examined ultrastructurally and morphometrically. RESULTS: The mean number of patent tubules, the mean area, perimeter and the area percent of the tubules were analyzed. Ultrastructurally, the dentinal tubules of both coronal and radicular dentin in the lathyritic group were narrower or even obliterated compared with those in the control. The coronal and radicular dentin of the lathyritic group exhibited an irregular lattice of non-mineralized small branching collagen fibrils obliterating the dentinal tubules. The mean number of patent tubules in the control and lathyritic groups revealed an insignificant difference. The mean area of the tubules showed a statistically significant difference in lathyritic radicular dentin (P = 0.0353). The percentage of the total surface area of the dentinal tubules significantly decreased in the radicular dentin of the lathyritic group (P = 0.024). CONCLUSIONS: These findings indicated a deleterious effect of lathyrism on dentin, with a possible negative impact on developing teeth integrity.

Multifocal odontoblastic dysplasia in a dog.

A two-year-old Boerboel dog presented for a discolored left maxillary canine tooth. Dental radiographs revealed abnormally mineralized pulp within the discolored tooth. Similar radiographic findings were also seen in both maxillary third incisor teeth and in the remaining canine teeth to varying degrees. The discolored tooth was treated by surgical extraction and histopathology revealed abnormal dentin deposition within the canal indicative of dentin dysplasia. Although not previously documented in the dog, the pulpal changes in multiple teeth of the dog reported here were similar to those described for odontoblastic dysplasia in humans. This case report includes a review of developmental abnormalities of dentin in humans and pulpal response to inflammation and injury.

[Dentinogenesis imperfecta: a developmental anomaly of the dentin in the primary dentition. A literature review].

This literature review summarizes the current knowledge about Dentinigenesis Imperfecta, a developmental anomaly of thedentin.The phenomenon's classification is presented in details, as well as its etiology, clinical, rentgenological and histological characteristics. In addition, the treatment modes are described.

VPS4B mutation impairs the osteogenic differentiation of dental follicle cells derived from a patient with dentin dysplasia type I.

A splicing mutation in VPS4B can cause dentin dysplasia type I (DD-I), a hereditary autosomal-dominant disorder characterized by rootless teeth, the etiology of which is genetically heterogeneous. In our study, dental follicle cells (DFCs) were isolated and cultured from a patient with DD-I and compared with those from an age-matched, healthy control. In a previous study, this DD-I patient was confirmed to have a loss-of-function splicing mutation in VPS4B (IVS7 + 46C > G). The results from this study showed that the isolated DFCs were vimentin-positive and CK14-negative, indicating that the isolated cells were derived from the mesenchyme. DFCs harboring the VPS4B mutation had a significantly higher proliferation rate from day 3 to day 8 than control DFCs, indicating that VPS4B is involved in cell proliferation. The cells were then replenished with osteogenic medium to investigate how the VPS4B mutation affected osteogenic differentiation. Induction of osteogenesis, detected by alizarin red and alkaline phosphatase staining in vitro, was decreased in the DFCs from the DD-I patient compared to the control DFCs. Furthermore, we also found that the VPS4B mutation in the DD-I patient downregulated the expression of osteoblast-related genes, such as ALP, BSP, OCN, RUNX2, and their encoded proteins. These outcomes confirmed that the DD-I-associated VPS4B mutation could decrease the capacity of DFCs to differentiate during the mineralization process and may also impair physiological root formation and bone remodeling. This might provide valuable insights and implications for exploring the pathological mechanisms underlying DD-I root development.

Dentin dysplasia type I.

This paper describes a rare case of genetically determined dentin dysplasia type Iin 26-year-old male patient. The paper highlights anatomical and radiologicalaspects of dental abnormalities and emphasizes the significance of the educationof both general practitioners and paediatricians as regards referring patients withdiagnosed dentin dysplasia for a multi-specialty therapy.

Spontaneous Development of Dental Dysplasia in Aged Parp-1 Knockout Mice.

Poly(ADP-ribose) polymerase (Parp)-1 catalyzes polyADP-ribosylation using NAD+ and is involved in the DNA damage response, genome stability, and transcription. In this study, we demonstrated that aged Parp-1-/- mouse incisors showed more frequent dental dysplasia in both ICR/129Sv mixed background and C57BL/6 strain compared to aged Parp-1+/+ incisors, suggesting that Parp-1 deficiency could be involved in development of dental dysplasia at an advanced age. Computed tomography images confirmed that dental dysplasia was observed at significantly higher incidences in Parp-1-/- mice. The relative calcification levels of Parp-1-/- incisors were higher in both enamel and dentin (p < 0.05). Immunohistochemical analysis revealed (1) Parp-1 positivity in ameloblasts and odontoblasts in Parp-1+/+ incisor, (2) weaker dentin sialoprotein positivity in dentin of Parp-1-/- incisor, and (3) bone sialoprotein positivity in dentin of Parp-1-/- incisor, suggesting ectopic osteogenic formation in dentin of Parp-1-/- incisor. These results indicate that Parp-1 deficiency promotes odontogenic failure in incisors at an advanced age. Parp-1 deficiency did not affect dentinogenesis during the development of mice, suggesting that Parp-1 is not essential in dentinogenesis during development but is possibly involved in the regulation of continuous dentinogenesis in the incisors at an advanced age.

Florid cemento-osseous dysplasia mimicking multiple periapical pathology--an endodontic dilemma.

A case of florid cemento-osseous dysplasia (COD) mimicking periapical pathology is presented. The fact that the patient's lesion failed to resolve three years after root canal therapy, in addition to the presence of a mixed radiolucency with discreet radiopacities, mandated a biopsy which (along with radiographic co-relation) confirmed the diagnosis of cemento-osseous dysplasia. This case report illustrates the point that periapical radiolucencies may represent benign fibro-osseous lesions that may be overlooked or result in unnecessary endodontic treatment.

A rare case diagnosed as dentin dysplasia type II.

According to their phenotypic features, the hereditary dentin defects in humans are categorized in two major classes: dentinogenesis imperfecta and dentin dysplasia. At its turn, the dentin dysplasia is subdivided in dentin dysplasia type I and dentin dysplasia type II, a milder clinical manifestation of the condition. Here we report the clinical and radiographic findings of dentin dysplasia type II in two members of a family, a young adult female and her mother. Except a mild shade change of the incisal margins in upper central incisors and left upper canine of the daughter no abnormal occlusal wear or crown shape change of the teeth were disclosed in both patients. However, confluent large pulp stones in the thistle-tube shaped pulp chambers and pulpal obliteration were a common finding. The condition was diagnosed as dentin dysplasia type II.

Dentin dysplasia type 1 - clinical management dilemmas: A case report of first-generation sufferers.

Dentine Dysplasia is a rare genetic condition. The treatment options and dilemmas associated with the condition remain undiscovered so far. This article highlights the variations in traits and challenges faced in the treatment of the cases.