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Journal of Dental Research Jun 2023Dentinogenesis imperfecta (DI) is the main orodental manifestation of osteogenesis imperfecta (OI) caused by or heterozygous pathogenic variants. Its prevalence varies...
Dentinogenesis imperfecta (DI) is the main orodental manifestation of osteogenesis imperfecta (OI) caused by or heterozygous pathogenic variants. Its prevalence varies according to the studied population. Here, we report the molecular analysis of 81 patients with OI followed at reference centers in Brazil and France presenting or variants. Patients were submitted to clinical and radiographic dental examinations to diagnose the presence of DI. In addition, a systematic literature search and a descriptive statistical analysis were performed to investigate OI/DI phenotype-genotype correlation in a worldwide sample. In our cohort, 50 patients had pathogenic variants, and 31 patients had variants. A total of 25 novel variants were identified. Overall, data from a total of 906 individuals with OI were assessed. Results show that DI was more frequent in severe and moderate OI cases. DI prevalence was also more often associated with (67.6%) than with variants (45.4%) because variants mainly lead to qualitative defects that predispose to DI more than quantitative defects. For the first time, 4 DI hotspots were identified. In addition, we showed that 1) glycine substitution by branched and charged amino acids in the α2(I) chain and 2) substitutions occurring in major ligand binding regions-MLRB2 in α1(I) and MLBR 3 in α2(I)-could significantly predict DI ( < 0.05). The accumulated variant data analysis in this study provides a further basis for increasing our comprehension to better predict the occurrence and severity of DI and appropriate OI patient management.
Topics: Humans; Collagen Type I; Collagen Type I, alpha 1 Chain; Dentinogenesis Imperfecta; Genetic Association Studies; Mutation; Osteogenesis Imperfecta
PubMed: 36951356
DOI: 10.1177/00220345231154569 -
Oral Surgery, Oral Medicine, Oral... Jun 2021Dentinogenesis imperfecta (DI) requires dental treatment. This study investigated the characteristics of DI teeth associated with osteogenesis imperfecta (OI) and COL1A2...
OBJECTIVE
Dentinogenesis imperfecta (DI) requires dental treatment. This study investigated the characteristics of DI teeth associated with osteogenesis imperfecta (OI) and COL1A2 mutations.
STUDY DESIGN
Whole exome and Sanger sequencing were performed. Three primary teeth (called "OIDI teeth") obtained from 3 unrelated COL1A2 patients were investigated and compared with 9 control teeth from age-matched healthy individuals using colorimetry, micro-computed tomography, Knoop microhardness, energy dispersive X-ray spectroscopy, scanning electron microscopy, and histology.
RESULTS
All patients were identified with heterozygous glycine substitutions in COL1A2. The COL1A2 mutations, c.1531G>T and c.2027G>T, were de novo, whereas c.3106G>C was inherited. OIDI1, 2, and 3 teeth had a substantial decrease in dentin microhardness and lightness. OIDI2 enamel microhardness was significantly reduced, whereas OIDI1 and 3 had enamel microhardness comparable to that of control individuals. The OIDI1 pulp cavity was large; OIDI2 was narrow; and OIDI3 was obliterated. OIDI1 and 3 had significantly higher carbon levels than those in control individuals. Numerous ectopic calcified masses, sparse and obstructed dentinal tubules, dentin holes, and collagen disorientation were observed.
CONCLUSIONS
OIDI teeth had reduced lightness and variable pulp morphology. Weak dentin, mineral disproportion, and abnormal ultrastructure could contribute to the brittleness of OIDI teeth and adhesive restoration failure. Here, we expand the phenotypic spectrum of COL1A2 mutations and raise awareness among dentists seeing patients with OI.
Topics: Collagen Type I; Dentin; Dentinogenesis Imperfecta; Humans; Mutation; Osteogenesis Imperfecta; X-Ray Microtomography
PubMed: 33737018
DOI: 10.1016/j.oooo.2021.01.003 -
British Dental Journal Sep 2022This paper examines the various contemporary clinical interfaces between paediatric dentistry and restorative dentistry for patients with both acquired and congenital...
This paper examines the various contemporary clinical interfaces between paediatric dentistry and restorative dentistry for patients with both acquired and congenital abnormalities presenting to primary and secondary care. Dental trauma of the child or adolescent has long-standing implications on future oral health due to conditions such as ankylosis, pulp necrosis, coronal tissue loss or tooth loss, all of which provide significant challenges into adulthood. Similarly, congenital conditions, such as hypodontia and structural deficiencies or malformations, such as amelogenesis and dentinogenesis imperfecta, result in the need for collaborative, multi-speciality decision-making from a young age, creating a pathway for longitudinal multi-disciplinary team treatment planning.
Topics: Adolescent; Adult; Amelogenesis Imperfecta; Anodontia; Child; Humans; Oral Health; Patient Care Planning; Pediatric Dentistry
PubMed: 36151172
DOI: 10.1038/s41415-022-4983-2 -
Pediatric and Developmental Pathology :... 2023Unique dental conditions in children include odontogenic cysts and tumors, hereditary dental diseases, developmental anomalies, and lesions associated with the eruption... (Review)
Review
Unique dental conditions in children include odontogenic cysts and tumors, hereditary dental diseases, developmental anomalies, and lesions associated with the eruption of the primary or permanent teeth. Many of these conditions have long lasting effects on the adult dentition in terms of affecting esthetics, function, and overall quality of life. Inherited dental syndromes affect the dental hard tissues specifically the enamel, dentin, and/or cementum in a generalized manner, involving both primary and permanent teeth. These conditions manifest in altered quality or quantity of the hard tissues, leading to fragility, tooth loss and dental diseases such as caries, periapical pathology, and periodontal disease. This category includes amelogenesis imperfecta, dentinogenesis imperfecta, dentin dysplasia, hypophosphatasia, and hypophosphatemia. Developmental defects such as regional odontodysplasia are defined by involvement of the primary and permanent dentition in a localized manner, identified in early childhood. This review will elaborate on the histologic findings in these selected dental conditions with a discussion on clinical and radiographic findings, as well as molecular features wherever appropriate.
Topics: Adult; Humans; Child, Preschool; Child; Quality of Life; Tooth; Amelogenesis Imperfecta; Syndrome
PubMed: 37962547
DOI: 10.1177/10935266231207045 -
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 -
Journal of Veterinary Dentistry Oct 2023Dentinogenesis imperfecta is a rare, autosomal dominant, hereditary disorder that occurs in humans and animals. In humans, known causative genetic mutations have been... (Review)
Review
Dentinogenesis imperfecta is a rare, autosomal dominant, hereditary disorder that occurs in humans and animals. In humans, known causative genetic mutations have been elucidated; however, veterinary literature on the topic is limited. This case report describes a 1-year-old female Labrador Retriever who presented for evaluation of generalized discoloration of the permanent dentition with historical discoloration of the deciduous dentition. Radiographic and histopathological findings will be discussed, as well as an in-depth review of the current human and veterinary literature pertaining to the pathogenesis and treatment options for dentinogenesis imperfecta.
PubMed: 37872656
DOI: 10.1177/08987564231208359 -
Journal of Dentistry Jun 2021A better understanding of the microstructure and mechanical properties of enamel and dentine may enable practitioners to apply the current adhesive dentistry protocols... (Review)
Review
OBJECTIVES
A better understanding of the microstructure and mechanical properties of enamel and dentine may enable practitioners to apply the current adhesive dentistry protocols to clinical cases involving dentine disorders (dentinogenesis imperfecta or dentine dysplasia).
DATA/SOURCES
Publications (up to June 2020) investigating the microstructure of dentine disorders were browsed in a systematic search using the PubMed/Medline, Embase and Cochrane Library electronic databases. Two authors independently selected the studies, extracted the data in accordance with the PRISMA statement, and assessed the risk of bias with the Critical Appraisal Checklist. A Mann-Whitney U test was computed to compare tissues damage related to the two dentine disorders of interest.
STUDY SELECTION
From an initial total of 642 studies, only 37 (n = 164 teeth) were included in the present analysis, among which 18 investigating enamel (n = 70 teeth), 15 the dentine-enamel junction (n = 62 teeth), and 35 dentine (n = 156 teeth). Dentine is damaged in cases of dentinogenesis imperfecta and osteogenesis imperfecta (p = 2.55E-21 and p = 3.99E-21, respectively). These studies highlight a reduction in mineral density, hardness, modulus of elasticity and abnormal microstructure in dentine disorders. The majority of studies report an altered dentine-enamel junction in dentinogenesis imperfecta and in osteogenesis imperfecta (p = 6.26E-09 and p = 0.001, respectively). Interestingly, enamel is also affected in cases of dentinogenesis imperfecta (p = 0.0013), unlike to osteogenesis imperfecta (p = 0.056).
CONCLUSIONS
Taking into account all these observations, only a few clinical principles may be favoured in the case of adhesive cementation: (i) to preserve the residual enamel to enhance bonding, (ii) to sandblast the tooth surfaces to increase roughness, (iii) to choose a universal adhesive and reinforce enamel and dentine by means of infiltrant resins. As these recommendations are mostly based on in vitro studies, future in vivo studies should be conducted to confirm these hypotheses.
Topics: Dental Cements; Dental Enamel; Dentin; Hardness; Tooth
PubMed: 33798638
DOI: 10.1016/j.jdent.2021.103654 -
Monographs in Oral Science 2023The development of the human dentition is prone to disruption due to its delicate and complex nature - including variations in tooth number and anatomical form and in... (Review)
Review
The development of the human dentition is prone to disruption due to its delicate and complex nature - including variations in tooth number and anatomical form and in the characteristics of enamel, dentine, and cementum. This chapter will focus on developmental defects of dental enamel (DDE) and dentine (DDD), which can be associated with considerable treatment burden on an individual, often related to the change in dental hard tissue characteristics in those at increased caries risk. DDE are prevalent and can be related to genetic conditions such as amelogenesis imperfecta and environmental challenges such as direct physical trauma to the developing tooth or systemic insults during the different phases of amelogenesis. Phenotypical variability can be great, making diagnosis difficult in many cases. There are two major enamel defects - the quantitative defect of hypoplasia and the qualitative defect of hypomineralization. DDDs are less prevalent than DDEs, with two major DDD types: dentinogenesis imperfecta and dentine dysplasia. The main features of the DDDs are enamel fracture exposing the dentine and subsequent wear, with enlarged pulp spaces in some variants. The appearance may be affected, with bulbous teeth and grey-blue to brown opalescent colouring. With respect to dental caries, developmental defects of the teeth, in themselves, do not cause caries risk; however, they can change the manifestation of the disease due to creating niches for biofilm accumulation and thereby increasing cleaning difficulty and changing the physical and chemical characteristics of dental hard tissues and how they react to cariogenic challenges.
Topics: Humans; Dental Caries; Dental Caries Susceptibility; Amelogenesis Imperfecta; Dental Enamel; Dentin
PubMed: 37364549
DOI: 10.1159/000530556 -
Clinical Oral Investigations Apr 2024Dentinogenesis imperfecta (DI) is an inherited dentin defect and may be isolated or associated with disorders such as osteogenesis imperfecta, odontochondrodysplasia...
OBJECTIVE
Dentinogenesis imperfecta (DI) is an inherited dentin defect and may be isolated or associated with disorders such as osteogenesis imperfecta, odontochondrodysplasia Ehler-Danlos and others. Isolated DI is caused mainly by pathogenic variants in DSPP gene and around 50 different variants have been described in this gene. Herein, we report on 19 patients from two unrelated Egyptian families with isolated DI. Additionally, we focused on genetic counselling of the two families.
MATERIALS AND METHODS
The patients were examined clinically and dentally. Panoramic X-rays were done to some patients. Whole exome sequencing (WES) and Sanger sequencing were used.
RESULTS
WES revealed two new nonsense variants in DSPP gene, c.288T > A (p.Tyr96Ter) and c.255G > A (p.Trp85Ter). Segregation analysis by Sanger sequencing confirmed the presence of the first variant in all affected members of Family 1 while the second variant was confirmed to be de novo in the patient of Family 2.
CONCLUSIONS AND CLINICAL RELEVANCE
Our study extends the number of DSPP pathogenic variants and strengthens the fact that DSPP is the most common DI causative gene irrespective of patients' ethnicity. In addition, we provide insights on genetic counseling issues in patients with inherited DSPP variants taking into consideration the variable religion, culture and laws in our society.
Topics: Humans; Dentinogenesis Imperfecta; Genetic Counseling; Ethnicity; Osteochondrodysplasias; Radiography, Panoramic
PubMed: 38630328
DOI: 10.1007/s00784-024-05636-z -
Global Medical Genetics Sep 2021Dentin sialophosphoprotein ( ) gene mutations cause autosomal dominantly inherited diseases. gene mutations lead to abnormal expression of DSPP, resulting in a series... (Review)
Review
Dentin sialophosphoprotein ( ) gene mutations cause autosomal dominantly inherited diseases. gene mutations lead to abnormal expression of DSPP, resulting in a series of histological, morphological, and clinical abnormalities. A large number of previous studies demonstrated that DSPP is a dentinal-specific protein, and gene mutations lead to dentin dysplasia and dentinogenesis imperfecta. Recent studies have found that DSPP is also expressed in bone, periodontal tissues, and salivary glands. DSPP is involved in the formation of the periodontium as well as tooth structures. DSPP deficient mice present furcation involvement, cementum, and alveolar bone defect. We speculate that similar periodontal damage may occur in patients with mutations. This article reviewed the effects of gene mutations on periodontal status. However, almost all of the research is about animal study, there is no evidence that mutations cause periodontium defects in patients yet. We need to conduct systematic clinical studies on mutation families in the future to elucidate the effect of gene on human periodontium.
PubMed: 34430959
DOI: 10.1055/s-0041-1726416