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International Journal of Clinical... 2019Dentinogenesis imperfect is a hereditary dentin defect leading to discoloration as well as early tooth wear. Timely diagnosis and treatment are required to prevent...
UNLABELLED
Dentinogenesis imperfect is a hereditary dentin defect leading to discoloration as well as early tooth wear. Timely diagnosis and treatment are required to prevent further tooth loss. Two patients reported to the department of pediatrics dentistry with dentinogenesis imperfecta (DI). In the first case, patient complained of discoloration of both primary and permanent teeth and delayed eruption of permanent teeth. In the second case report, patient reported with mobile anterior tooth and missing teeth due to extraction of mobile teeth. Extraction was followed by space maintainers in the first case, and extraction was followed by partial denture in the second case. Both the patients and their parents were happy with the treatment provided.
HOW TO CITE THIS ARTICLE
Kaur A, Kumar S, Karda B, Management of Dentinogenesis Imperfecta: A Report of Two Cases. Int J Clin Pediatr Dent 2019;12(5):464-466.
PubMed: 32440055
DOI: 10.5005/jp-journals-10005-1681 -
Journal of Bone and Mineral Research :... Aug 2020Osteogenesis imperfecta (OI) is a primary bone fragility disorder with an estimated prevalence of 1 in 15,000 births. The majority of OI cases are inherited in an...
Osteogenesis imperfecta (OI) is a primary bone fragility disorder with an estimated prevalence of 1 in 15,000 births. The majority of OI cases are inherited in an autosomal-dominant manner, while 5% to 10% have recessive or X-linked inheritance. Up to now, approximately 5% of OI cases remain without mutation demonstrated, supporting the involvement of other genes in the disease spectrum. By whole-exome sequencing, we identified a homozygous variant (c.2T>C) in CCDC134 gene in three patients from two unrelated families with severe bone fragility that did not respond to bisphosphonate treatment, short stature, and gracile long bones with pseudarthroses but no dentinogenesis imperfecta. CCDC134 encodes a secreted protein widely expressed and implicated in the regulation of some mitogen-activated protein kinases (MAPK) signaling pathway. Western blot and immunofluorescence analyses confirmed the absence of CCDC134 protein in patient cells compared with controls. Furthermore, we demonstrated that CCDC134 mutations are associated with increased Erk1/2 phosphorylation, decreased OPN mRNA and COL1A1 expression and reduced mineralization in patient osteoblasts compared with controls. These data support that CCDC134 is a new gene involved in severe progressive deforming recessive osteogenesis imperfecta (type III). © 2020 American Society for Bone and Mineral Research.
Topics: Bone and Bones; Collagen Type I; Homozygote; Humans; Loss of Function Mutation; Membrane Proteins; Osteogenesis Imperfecta; Exome Sequencing
PubMed: 32181939
DOI: 10.1002/jbmr.4011 -
Acta Dermato-venereologica Mar 2020Ehlers-Danlos syndromes (EDS) are a group of inherited connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and variable tissue...
Ehlers-Danlos syndromes (EDS) are a group of inherited connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and variable tissue fragility. However, there are limited published data on the dental manifestations of EDS. This review systematically assessed the spectrum of published dental anomalies in various types of EDS. Twenty-four individual case reports/series and 3 longer case-control studies, reporting on a total of 84 individuals with a clinical diagnosis of EDS, were included in the data analysis. The main dental features listed in classical EDS were pulp calcification and localized root hypoplasia. Common dental abnormalities observed in vascular EDS were pulp shape modifications (52.2%), exceeding root length (34.8%), and molar root fusion (47.8%). Dentinogenesis imperfecta is a consistent finding in osteogenesis imperfecta/EDS overlap syndrome. Data on dental manifestations in other types of EDS are both rare and generally inconclusive.
Topics: Dental Pulp Calcification; Ehlers-Danlos Syndrome; Humans; Tooth Abnormalities; Tooth Diseases; Tooth Root
PubMed: 32147746
DOI: 10.2340/00015555-3428 -
ELife Feb 2020The transport and Golgi organization 1 (TANGO1) proteins play pivotal roles in the secretory pathway. Full length TANGO1 is a transmembrane protein localised at...
The transport and Golgi organization 1 (TANGO1) proteins play pivotal roles in the secretory pathway. Full length TANGO1 is a transmembrane protein localised at endoplasmic reticulum (ER) exit sites, where it binds bulky cargo within the ER lumen and recruits membranes from the ER Golgi intermediate compartment to create an exit route for their export. Here we report the first TANGO1-associated syndrome in humans. A synonymous substitution that results in exon eight skipping in most mRNA molecules, ultimately leading to a truncated TANGO1 protein was identified as disease-causing mutation. The four homozygously affected sons of a consanguineous family display severe dentinogenesis imperfecta, short stature, various skeletal abnormalities, insulin-dependent diabetes mellitus, sensorineural hearing loss, and mild intellectual disability. Functional studies in HeLa and U2OS cells revealed that the corresponding truncated TANGO1 protein is dispersed in the ER and its expression in cells with intact endogenous TANGO1 impairs cellular collagen I secretion.
Topics: Alleles; Aryl Hydrocarbon Receptor Nuclear Translocator; Cell Line, Tumor; Collagen; Endoplasmic Reticulum; Enhancer Elements, Genetic; Exons; Golgi Apparatus; Humans; Mutation; Protein Transport; Exome Sequencing
PubMed: 32101163
DOI: 10.7554/eLife.51319 -
BMC Musculoskeletal Disorders Jan 2020Osteogenesis Imperfecta (OI) is characterized by bone fragility, and features such as blue sclerae, dentinogenesis imperfecta, hearing loss, ligamentous laxity and short...
BACKGROUND
Osteogenesis Imperfecta (OI) is characterized by bone fragility, and features such as blue sclerae, dentinogenesis imperfecta, hearing loss, ligamentous laxity and short stature can be present. It has long been assumed that the functional ability and quality of life of patients with OI depends primarily on the severity of skeletal deformities. However, fatigue is often mentioned in clinic by patients with all types of OI as an important modifier of their quality of life and does not always seem to be related to their functional ability. The aim of this study is to investigate whether adults with Osteogenesis Imperfecta are significantly more fatigued than the normal population.
METHODS
The Fatigue Severity Scale (FSS) was distributed by mobile phone application among 151 adult patients with different OI types. Results of the FSS in the OI group were compared with two control populations from America (n = 20) and the Netherlands (n = 113).
RESULTS
Ninety-nine patients (OI type 1 (n = 72), OI type 3 (n = 13), OI type 4 (n = 14) completed the FSS questionnaire. The mean FSS score of this cohort was 4.4 and significantly higher than the control populations (2.3/2.9). 65% of our cohort reported at least moderate fatigue compared with 2 control populations from America and the Netherlands.
CONCLUSION
Fatigue in patients with OI is a frequently encountered problem in our expert clinic but research into this topic is sparse. This pilot study is the largest study to date investigating fatigue in patients with OI and results have been compared with two control groups. The mean FSS score of 4.4 in the OI group indicates that people with OI are generally significantly more fatigued than the control population. Further evaluation of fatigue and its influencers in a larger group of OI patients is important for future management.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Case-Control Studies; Cell Phone; Cost of Illness; Cross-Sectional Studies; Fatigue; Female; Health Status; Humans; Male; Middle Aged; Mobile Applications; Osteogenesis Imperfecta; Pilot Projects; Predictive Value of Tests; Quality of Life; Severity of Illness Index; Surveys and Questionnaires; Young Adult
PubMed: 31900144
DOI: 10.1186/s12891-019-3000-7 -
Journal of Oral Biosciences Mar 2020The Bone Morphogenetic Proteins (BMPs) direct tooth development and still express in the adult tooth. We hypothesized that inhibition of BMP function would therefore...
OBJECTIVES
The Bone Morphogenetic Proteins (BMPs) direct tooth development and still express in the adult tooth. We hypothesized that inhibition of BMP function would therefore disrupt dentinogenesis by differentiated odontoblasts.
METHODS
We generated mice overexpressing the BMP-inhibitory protein Noggin in differentiated odontoblasts and osteocytes under control of a Dmp1 promoter-driven cre transgene. We compared the dentin phenotype in these mice with that in WT littermates and in mice with a Smad4 odontoblast/osteocyte knockout mediated by the same cre and therefore lacking all BMP and Tgfβ signaling in the same tissues.
RESULTS
Three-month-old first molars from both Noggin-expressing and Smad4-deleted mice showed decreased dentin volume with enlarged pulp cavities, and both displayed less organized and mineralized dentinal tubules compared to WT. The Smad4-ablated phenotype was more severe. While dentin sialophosphoprotein (DSPP) and bone sialoprotein (BSP) were decreased in the dentin of both lines, dentin matrix protein 1 (DMP1) was sharply increased in Noggin-expressing teeth.
CONCLUSIONS
The phenotypes we observed in Noggin-overexpressing and Smad4-conditional knockout teeth resemble the phenotype of Dentinogenesis Imperfecta (DGI) type III. Our results show that BMPs regulate post-natal dentinogenesis and that BMP-inhibitory proteins like Noggin play a role in that regulation. The increased severity of the Smad4 phenotype indicates that Tgfβ ligands, in addition to BMPs, play a crucial role in post-developmental dentinogenesis.
Topics: Animals; Carrier Proteins; Dentin; Dentinogenesis; Extracellular Matrix Proteins; Mice; Phosphoproteins; Sialoglycoproteins
PubMed: 31862386
DOI: 10.1016/j.job.2019.11.001 -
European Archives of Paediatric... Aug 2020To analyse the elemental composition of dentine in primary teeth from children diagnosed with Dentinogenesis Imperfecta type II (DI) and from normal sound primary teeth...
AIM
To analyse the elemental composition of dentine in primary teeth from children diagnosed with Dentinogenesis Imperfecta type II (DI) and from normal sound primary teeth using X-ray microanalysis.
MATERIALS AND METHODS
X-ray microanalysis of the elements C, O, Na, Mg, P, Cl, K and Ca were performed in the dentine of five normal primary teeth and in seven primary teeth diagnosed DI. The analysis was made in a low magnification in 10 points from the enamel-dentine junction/root surface toward the pulp. The data was also evaluated with an inductive analysis.
RESULTS
Lower values for C were found in DI-dentine compared with normal dentine. Na had significantly higher values in DI-dentine while Mg had significantly lower values. The inductive analysis revealed that Na and Mg were the most important elements for discriminating DI-dentine from normal dentine.
CONCLUSIONS
Dentine in primary teeth from patients diagnosed with Dentinogenesis Imperfecta type II analysed with XRMA have lower values of C and Mg and higher values of O and Na compared with normal primary dentine.
Topics: Child; Dental Enamel; Dentin; Dentinogenesis Imperfecta; Electron Probe Microanalysis; Humans; Tooth, Deciduous
PubMed: 31823211
DOI: 10.1007/s40368-018-0392-2 -
International Journal of Nanomedicine 2019Dentinogenesis imperfecta type 1 (OIDI) is considered a relatively rare genetic disorder (1:5000 to 1:45,000) associated with osteogenesis imperfecta. OIDI impacts the...
INTRODUCTION
Dentinogenesis imperfecta type 1 (OIDI) is considered a relatively rare genetic disorder (1:5000 to 1:45,000) associated with osteogenesis imperfecta. OIDI impacts the formation of collagen fibrils in dentin, leading to morphological and structural changes that affect the strength and appearance of teeth. However, there is still a lack of understanding regarding the nanoscale characterization of the disease, in terms of collagen ultrastructure and mechanical properties. Therefore, this research presents a qualitative and quantitative report into the phenotype and characterization of OIDI in dentin, by using a combination of imaging, nanomechanical approaches.
METHODS
For this study, 8 primary molars from OIDI patients and 8 primary control molars were collected, embedded in acrylic resin and cut into longitudinal sections. Sections were then demineralized in 37% phosphoric acid using a protocol developed in-house. Initial experiments demonstrated the effectiveness of the demineralization protocol, as the ATR-FTIR spectral fingerprints showed an increase in the amide bands together with a decrease in phosphate content. Structural and mechanical analyses were performed directly on both the mineralized and demineralized samples using a combination of scanning electron microscopy, atomic force microscopy, and Wallace indentation.
RESULTS
Mesoscale imaging showed alterations in dentinal tubule morphology in OIDI patients, with a reduced number of tubules and a decreased tubule diameter compared to healthy controls. Nanoscale collagen ultrastructure presented a similar D-banding periodicity between OIDI and controls. Reduced collagen fibrils diameter was also recorded for the OIDI group. The hardness of the (mineralized) control dentin was found to be significantly higher (p<0.05) than that of the OIDI (mineralized) dentine. Both the exposed peri- and intratubular dentinal collagen presented bimodal elastic behaviors (Young's moduli). The control samples presented a stiffening of the intratubular collagen when compared to the peritubular collagen. In case of the OIDI, this stiffening in the collagen between peri- and intratubular dentinal collagen was not observed and the exposed collagen presented overall a lower elasticity than the control samples.
CONCLUSION
This study presents a systematic approach to the characterization of collagen structure and properties in OIDI as diagnosed in dentin. Structural markers for OIDI at the mesoscale and nanoscale were found and correlated with an observed lack of increased elastic moduli of the collagen fibrils in the intratubular OIDI dentin. These findings offer an explanation of how structural changes in the dentin could be responsible for the failure of some adhesive restorative materials as observed in patients affected by OIDI.
Topics: Collagen; Dentin; Dentinogenesis Imperfecta; Elasticity; Hardness; Humans; Molar; Osteogenesis Imperfecta; Phenotype; Radiography, Bitewing; Spectroscopy, Fourier Transform Infrared; Tooth Demineralization
PubMed: 31819441
DOI: 10.2147/IJN.S217420 -
Indian Journal of Dental Research :... 2019Dentinogenesis Imperfecta and dentin dysplasia are genetic oral diseases inherited in a simple autosomal dominant mode, with high penetrance and a low mutation rate.... (Review)
Review
Dentinogenesis Imperfecta and dentin dysplasia are genetic oral diseases inherited in a simple autosomal dominant mode, with high penetrance and a low mutation rate. Both of them are present with bulbous crowns, marked cervical constrictions, severe attritions, few periapical radiolucencies, and premature tooth loss. The diagnosis is based on family history, and detailed clinical examination, while genetic diagnosis may become useful in the future once sufficient disease-causing mutations have been discovered. Here, we present a case with overlapping features of both dentinogenesis imperfecta and dentin dysplasia asserting both the anomalies to be part of the same continuum of the genetic event.
Topics: Dentin; Dentin Dysplasia; Dentinogenesis Imperfecta; Extracellular Matrix Proteins; Humans; Pedigree; Phosphoproteins; Sialoglycoproteins
PubMed: 31745067
DOI: 10.4103/ijdr.IJDR_318_18 -
Frontiers in Pharmacology 2019Osteogenesis imperfecta (OI), mainly caused by structural abnormalities of type I collagen, is a hereditary rare disease characterized by increased bone fragility and...
Osteogenesis imperfecta (OI), mainly caused by structural abnormalities of type I collagen, is a hereditary rare disease characterized by increased bone fragility and reduced bone mass. Clinical manifestations of OI mostly include multiple repeated bone fractures, thin skin, blue sclera, hearing loss, cardiovascular and pulmonary system abnormalities, triangular face, dentinogenesis imperfecta (DI), and walking with assistance. Currently, 20 causative genes with 18 subtypes have been identified for OI, of them, variations in and have been demonstrated to be major causative factors to OI. However, the complexity of the bone formation process indicates that there are potential new pathogenic genes associated with OI. To comprehensively explore the underlying mechanism of OI, we conducted association analysis between genotypes and phenotypes of OI diseases and found that mutations in and contributed to a large proportion of the disease phenotypes. We categorized the clinical phenotypes and the genotypes based on the variation types for those 155 OI patients collected from literature, and association study revealed that three phenotypes (bone deformity, DI, walking with assistance) were enriched in two variation types (the Gly-substitution missense and groups of frameshift, nonsense, and splicing variations). We also identified four novel variations (c.G3290A (p.G1097D), c.G3289C (p.G1097R), c.G3289A (p.G1097S), c.G3281A (p.G1094D)) in gene and two novel variations (c.G2332T (p.G778C), c.G2341T (p.G781C)) in gene , which could potentially contribute to the disease. In addition, we identified several new potential pathogenic genes (, , ) based on the integration of protein-protein interaction and pathway enrichment analysis. Our study provides new insights into the association between genotypes and phenotypes of OI and novel information for dissecting the underlying mechanism of the disease.
PubMed: 31680973
DOI: 10.3389/fphar.2019.01200