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Monographs in Oral Science 2021Mutations in several genes can lead to amelogenesis imperfecta. These same genes and other members of their pathways quite possibly may also contribute to individual... (Review)
Review
Mutations in several genes can lead to amelogenesis imperfecta. These same genes and other members of their pathways quite possibly may also contribute to individual susceptibility to dental caries and/or erosive tooth wear. This chapter provides an analysis of the function of the genes which, when mutated, cause amelogenesis imperfecta and discusses how mechanisms involving hypomorphic alleles in one or more genes, methylation changes, and imprinting disorders could be underlying individual susceptibility to dental caries and/or erosive tooth wear.
Topics: Amelogenesis Imperfecta; Dental Caries; Humans; Mutation; Tooth Wear
PubMed: 35078171
DOI: 10.1159/000520764 -
Oral Diseases Sep 2023Amelogenesis imperfecta (AI) is one of the typical dental genetic diseases in human. It can occur isolatedly or as part of a syndrome. Previous reports have mainly... (Review)
Review
Amelogenesis imperfecta (AI) is one of the typical dental genetic diseases in human. It can occur isolatedly or as part of a syndrome. Previous reports have mainly clarified the types and mechanisms of nonsyndromic AI. This review aimed to compare the phenotypic differences among the hereditary enamel defects with or without syndromes and their underlying pathogenic genes. We searched the articles in PubMed with different strategies or keywords including but not limited to amelogenesis imperfecta, enamel defects, hypoplastic/hypomaturation/hypocalcified, syndrome, or specific syndrome name. The articles with detailed clinical information about the enamel and other phenotypes and clear genetic background were used for the analysis. We totally summarized and compared enamel phenotypes of 18 nonsyndromic AI with 17 causative genes and 19 syndromic AI with 26 causative genes. According to the clinical features, radiographic or ultrastructural changes in enamel, the enamel defects were basically divided into hypoplastic and hypomineralized (hypomaturated and hypocalcified) and presented a higher heterogeneity which were closely related to the involved pathogenic genes, types of mutation, hereditary pattern, X chromosome inactivation, incomplete penetrance, and other mechanisms.The gene-specific enamel phenotypes could be an important indicator for diagnosing nonsyndromic and syndromic AI.
Topics: Humans; Amelogenesis Imperfecta; Dental Enamel; Dental Enamel Hypoplasia; Dental Enamel Proteins; Phenotype
PubMed: 37154292
DOI: 10.1111/odi.14599 -
International Orthodontics Dec 2023The aim of this systematic review (Prospero CRD42022323188) is to investigate whether an association exists in patients with amelogenesis imperfecta (AI) between...
INTRODUCTION
The aim of this systematic review (Prospero CRD42022323188) is to investigate whether an association exists in patients with amelogenesis imperfecta (AI) between occlusal characteristics and genotype on the one hand and enamel structural phenotype on the other.
MATERIAL AND METHODS
Reports up to May 2023 assessing occlusion of individuals with AI were browsed in a systematic search using Medline, Embase, ISI Web of Science, and the grey literature. Randomised control trials, case control studies, and case series specifying both occlusion, assessed by cephalometric or clinical analysis, and genotype or dental phenotype in patients with AI were included without any age limitation. Two authors independently selected the publications and extracted the data in accordance with the PRISMA statement. The risk of bias was assessed with the Critical Appraisal Checklists from the Johanna Briggs Institute.
RESULTS
Twenty-five articles were chosen from the 261 results. Most of the included publications were case series (n=22) and case control studies (n=3). Thirteen studies reported both a genotype (ENAM, FAM83H, FAM20A, DLX3, CNMM4, WDR72) and occlusal diagnostic. The methodological quality of the studies was moderate. All AI phenotypes showed an open bite (OB) rate around 35%, except mixed form. The other malocclusions were not often mentioned. No correlation between occlusal phenotype and genotype or AI phenotype could be identified in patients with AI, as most studies had short occlusal descriptions and small sample sizes.
CONCLUSION
OB malocclusions were more frequently reported in AI. This review highlighted the need for a more accurate description of orofacial features associated with AI, to better clarify the role of amelogenesis genes in the regulation of craniofacial morphogenesis and identify patients requiring orthognathic surgery at an early stage.
Topics: Humans; Amelogenesis Imperfecta; Genotype; Phenotype; Dental Enamel; Malocclusion; Open Bite; Proteins
PubMed: 37494776
DOI: 10.1016/j.ortho.2023.100789 -
Journal of Dental Research Jun 2015Enamel is unique. It is the only epithelial-derived mineralized tissue in mammals and has a distinct micro- and nanostructure with nanofibrous apatite crystals as... (Review)
Review
Enamel is unique. It is the only epithelial-derived mineralized tissue in mammals and has a distinct micro- and nanostructure with nanofibrous apatite crystals as building blocks. It is synthesized by a highly specialized cell, the ameloblast, which secretes matrix proteins with little homology to any other known amino acid sequence, but which is composed of a primary structure that makes it competent to self-assemble and control apatite crystal growth at the nanometer scale. The end-product of ameloblast activity is a marvel of structural engineering: a material optimized to provide the tooth with maximum biting force, withstanding millions of cycles of loads without catastrophic failure, while also protecting the dental pulp from bacterial attack. This review attempts to bring into context the mechanical behavior of enamel with the developmental process of amelogenesis and structural development, since they are linked to tissue function, and the importance of controlling calcium phosphate mineralization at the nanometer scale. The origins of apatite nanofibers, the development of a stiffness gradient, and the biological processes responsible for the synthesis of a hard and fracture-resistant dental tissue are discussed with reference to the evolution of enamel from a fibrous composite to a complex, tough, and damage-tolerant coating on dentin.
Topics: Ameloblasts; Amelogenesis; Apatites; Biomechanical Phenomena; Calcium Phosphates; Crystallization; Dental Enamel; Dental Enamel Proteins; Humans; Nanofibers; Tooth Calcification
PubMed: 25800708
DOI: 10.1177/0022034515577963 -
Genes Feb 2023Dental enamel is a specialized tissue that has adapted over millions of years of evolution to enhance the survival of a variety of species. In humans, enamel evolved to... (Review)
Review
Dental enamel is a specialized tissue that has adapted over millions of years of evolution to enhance the survival of a variety of species. In humans, enamel evolved to form the exterior protective layer for the crown of the exposed tooth crown. Its unique composition, structure, physical properties and attachment to the underlying dentin tissue allow it to be a resilient, although not self-repairing, tissue. The process of enamel formation, known as amelogenesis, involves epithelial-derived cells called ameloblasts that secrete a unique extracellular matrix that influences the structure of the mineralizing enamel crystallites. There are over 115 known genetic conditions affecting amelogenesis that are associated with enamel phenotypes characterized by either a reduction of enamel amount and or mineralization. Amelogenesis involves many processes that are sensitive to perturbation and can be altered by numerous environmental stressors. Genetics, epigenetics, and environment factors can influence enamel formation and play a role in resistance/risk for developmental defects and the complex disease, dental caries. Understanding why and how enamel is affected and the enamel phenotypes seen clinically support diagnostics, prognosis prediction, and the selection of treatment approaches that are appropriate for the specific tissue defects (e.g., deficient amount, decreased mineral, reduced insulation and hypersensitivity). The current level of knowledge regarding the heritable enamel defects is sufficient to develop a new classification system and consensus nosology that effectively communicate the mode of inheritance, molecular defect/pathway, and the functional aberration and resulting enamel phenotype.
Topics: Humans; Dental Caries; Tooth; Ameloblasts; Phenotype; Dental Enamel
PubMed: 36980818
DOI: 10.3390/genes14030545 -
Journal of Dental Research Aug 2023Tooth enamel is generated by ameloblasts. Any failure in amelogenesis results in defects in the enamel, a condition known as amelogenesis imperfecta. Here, we report...
Tooth enamel is generated by ameloblasts. Any failure in amelogenesis results in defects in the enamel, a condition known as amelogenesis imperfecta. Here, we report that mice with deficient autophagy in epithelial-derived tissues ( and conditional knockout mice) exhibit amelogenesis imperfecta. Micro-computed tomography imaging confirmed that enamel density and thickness were significantly reduced in the teeth of these mice. At the molecular level, ameloblast differentiation was compromised through ectopic accumulation and activation of NRF2, a specific substrate of autophagy. Through bioinformatic analyses, we identified , , , , , and as candidate genes related to amelogenesis imperfecta and the NRF2-mediated pathway. To investigate the effects of the ectopic NRF2 pathway activation caused by the autophagy deficiency, we analyzed target gene expression and NRF2 binding to the promoter region of candidate target genes and found suppressed gene expression of , , , and but not of and . Taken together, our findings indicate that autophagy plays a crucial role in ameloblast differentiation and that its failure results in amelogenesis imperfecta through ectopic NRF2 activation.
Topics: Mice; Animals; Ameloblasts; Amelogenesis Imperfecta; X-Ray Microtomography; NF-E2-Related Factor 2; Amelogenesis; Mice, Knockout; Tumor Suppressor Proteins; Repressor Proteins
PubMed: 37249312
DOI: 10.1177/00220345231169220 -
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 -
Proceedings of the National Academy of... Dec 2022The outstanding mechanical and chemical properties of dental enamel emerge from its complex hierarchical architecture. An accurate, detailed multiscale model of the...
The outstanding mechanical and chemical properties of dental enamel emerge from its complex hierarchical architecture. An accurate, detailed multiscale model of the structure and composition of enamel is important for understanding lesion formation in tooth decay (dental caries), enamel development (amelogenesis) and associated pathologies (e.g., amelogenesis imperfecta or molar hypomineralization), and minimally invasive dentistry. Although features at length scales smaller than 100 nm (individual crystallites) and greater than 50 µm (multiple rods) are well understood, competing field of view and sampling considerations have hindered exploration of mesoscale features, i.e., at the level of single enamel rods and the interrod enamel (1 to 10 µm). Here, we combine synchrotron X-ray diffraction at submicrometer resolution, analysis of crystallite orientation distribution, and unsupervised machine learning to show that crystallographic parameters differ between rod head and rod tail/interrod enamel. This variation strongly suggests that crystallites in different microarchitectural domains also differ in their composition. Thus, we use a dilute linear model to predict the concentrations of minority ions in hydroxylapatite (Mg and CO/Na) that plausibly explain the observed lattice parameter variations. While differences within samples are highly significant and of similar magnitude, absolute values and the sign of the effect for some crystallographic parameters show interindividual variation that warrants further investigation. By revealing additional complexity at the rod/interrod level of human enamel and leaving open the possibility of modulation across larger length scales, these results inform future investigations into mechanisms governing amelogenesis and introduce another feature to consider when modeling the mechanical and chemical performance of enamel.
Topics: Humans; Dental Caries; Crystallography; Amelogenesis Imperfecta; Amelogenesis; Dental Enamel
PubMed: 36534796
DOI: 10.1073/pnas.2211285119 -
Calcified Tissue International Nov 2017Amelogenesis (tooth enamel formation) is a biomineralization process consisting primarily of two stages (secretory stage and maturation stage) with unique features.... (Review)
Review
Amelogenesis (tooth enamel formation) is a biomineralization process consisting primarily of two stages (secretory stage and maturation stage) with unique features. During the secretory stage, the inner epithelium of the enamel organ (i.e., the ameloblast cells) synthesizes and secretes enamel matrix proteins (EMPs) into the enamel space. The protein-rich enamel matrix forms a highly organized architecture in a pH-neutral microenvironment. As amelogenesis transitions to maturation stage, EMPs are degraded and internalized by ameloblasts through endosomal-lysosomal pathways. Enamel crystallite formation is initiated early in the secretory stage, however, during maturation stage the more rapid deposition of calcium and phosphate into the enamel space results in a rapid expansion of crystallite length and mineral volume. During maturation-stage amelogenesis, the pH value of enamel varies considerably from slightly above neutral to acidic. Extracellular acid-base balance during enamel maturation is tightly controlled by ameloblast-mediated regulatory networks, which include significant synthesis and movement of bicarbonate ions from both the enamel papillary layer cells and ameloblasts. In this review we summarize the carbonic anhydrases and the carbonate transporters/exchangers involved in pH regulation in maturation-stage amelogenesis. Proteins that have been shown to be instrumental in this process include CA2, CA6, CFTR, AE2, NBCe1, SLC26A1/SAT1, SLC26A3/DRA, SLC26A4/PDS, SLC26A6/PAT1, and SLC26A7/SUT2. In addition, we discuss the association of miRNA regulation with bicarbonate transport in tooth enamel formation.
Topics: Amelogenesis; Animals; Anion Transport Proteins; Bicarbonates; Biological Transport; Carbonic Anhydrases; Chloride-Bicarbonate Antiporters; Cystic Fibrosis Transmembrane Conductance Regulator; Dental Enamel; Humans; MicroRNAs; Sodium-Bicarbonate Symporters
PubMed: 28795233
DOI: 10.1007/s00223-017-0311-2 -
Special Care in Dentistry : Official... May 2018to describe a case in which dental changes were observed and investigation proceeded to consider Enamel-Renal-Syndrome (ERS), a rare disorder that associates...
AIMS
to describe a case in which dental changes were observed and investigation proceeded to consider Enamel-Renal-Syndrome (ERS), a rare disorder that associates amelogenesis imperfecta with nephrocalcinosis.
CASE REPORT
an 11-year-old male patient upon intraoral examination revealed generalized gingival hyperplasia, a few teeth were absent clinically and the remaining ones were yellowish-brown in color. The enamel alterations were suggesting of amelogenesis imperfecta. Unerupted teeth with increased pericoronal spaces, suggesting hyperplasic follicles or dentigerous cysts and an enamel with lower thickness and density were observed in the panoramic radiography. The patient was referred for an assay to investigate mucopolysaccharidosis; however, it was negative. A renal ultrasound showed bilateral nephrocalcinosis and laboratory exams, including calcium, phosphate, and creatinine levels were below the average. An incisional gingival biopsy showed numerous round to ovoid basophilic calcifications in the connective tissue. The final diagnosis was ERS.
CONCLUSION
Dentists should refer patients with similar clinical presentation for renal ultrasound evaluation in order to rule out the possible diagnosis of ERS.
Topics: Amelogenesis Imperfecta; Biopsy; Cephalometry; Child; Diagnosis, Differential; Humans; Male; Nephrocalcinosis; Radiography, Panoramic; Ultrasonography
PubMed: 29672880
DOI: 10.1111/scd.12288