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Cureus Dec 2023Amelogenesis imperfecta (AI) is a rare genetic disorder affecting children and adults. Knowledge about AI is limited to clinical representation and radiographical... (Review)
Review
Amelogenesis imperfecta (AI) is a rare genetic disorder affecting children and adults. Knowledge about AI is limited to clinical representation and radiographical findings. Various treatments are provided to children with AI, yet no definitive treatment guideline has been suggested in the literature. This scoping review highlights the knowledge of the etiology and classification of AI and synthesizes these findings in a comprehensive review, focusing mainly on the various forms of AI in children and management with a restorative conservative approach. Five electronic databases, namely, PubMed, Google Scholar, Embase, Web of Science, and Scopus, were searched for the relevant articles. The search was performed in two phases: first for title and abstract, and second for full-text articles. The studies included in this scoping review were published from 2013 to August 2023. The data extraction was done on a customized sheet. A total of 33 studies were included in this review, of which 19 were reports and series, seven were observational, and seven were reviews. Most patients included in this review suffered from the hypoplastic type of AI (54%), followed by hypomatured (36%), and hypocalcified (10%). The treatment modalities explained were divided into the following three phases: temporary, transient, and permanent. Almost all included reports suggested the requirement for guidelines for treating AI among young children. This scoping review suggests the need for guidelines for treating AI in children. Moreover, pediatric dentists should prioritize early diagnosis and treatment and long-term follow-up for AI in children to effectively enhance the patient's psychological well-being and overall quality of life.
PubMed: 38179349
DOI: 10.7759/cureus.49968 -
International Journal of Dentistry 2021Dentinogenesis imperfecta (DI) and amelogenesis imperfecta (AI) are hereditary abnormalities of dental hard tissues. Dental abnormalities may also be accompanied by... (Review)
Review
Dentinogenesis imperfecta (DI) and amelogenesis imperfecta (AI) are hereditary abnormalities of dental hard tissues. Dental abnormalities may also be accompanied by symptoms of disorders such as osteogenesis imperfecta. AI and DI have a significant burden on socializing, function, and comfort; therefore, frequent screening and accurate diagnosis is the cornerstone of managing such conditions. Both AI and DI could be treated with many strategies, including restorative, prosthetic, periodontal, surgical, and orthodontics treatment. The interdisciplinary combination of orthodontic, prosthodontic, and periodontic treatment has been proven to improve the prognosis of AI and DI. Regarding orthodontic treatment, the most difficult element of orthodontic therapy may be maintaining a high level of motivation for what might be a prolonged form of treatment spanning several years. There are many forms of orthodontic management for AI and DI, including removable appliances, functional appliances, and fixed appliances. Clear aligner therapy (CAT) contains a broad range of equipment that works in different ways, has different construction processes, and is compatible with different malocclusion procedures. The application of CAT in patients with AI and DI is favorable over the fixed applicants. However, the available evidence regarding the application of CAT in AI is weak and heterogeneous. In this review, we discussed the current evidence regarding the application of clear CAT in patients with AI and DI.
PubMed: 34976063
DOI: 10.1155/2021/7343094 -
Journal of Dental Research Oct 2023Amelogenin plays a crucial role in tooth enamel formation, and mutations on X-chromosomal amelogenin cause X-linked amelogenesis imperfecta (AI). Amelogenin...
Amelogenin plays a crucial role in tooth enamel formation, and mutations on X-chromosomal amelogenin cause X-linked amelogenesis imperfecta (AI). Amelogenin pre-messenger RNA (mRNA) is highly alternatively spliced, and during alternative splicing, exon4 is mostly skipped, leading to the formation of a microRNA (miR-exon4) that has been suggested to function in enamel and bone formation. While delivering the functional variation of amelogenin proteins, alternative splicing of exon4 is the decisive first step to producing miR-exon4. However, the factors that regulate the splicing of exon4 are not well understood. This study aimed to investigate the association between known mutations in exon4 and exon5 of X chromosome amelogenin that causes X-linked AI, the splicing of exon4, and miR-exon4 formation. Our results showed mutations in exon4 and exon5 of the amelogenin gene, including c.120T>C, c.152C>T, c.155C>G, and c.155delC, significantly affected the splicing of exon4 and subsequent miR-exon4 production. Using an amelogenin minigene transfected in HEK-293 cells, we observed increased inclusion of exon4 in amelogenin mRNA and reduced miR-exon4 production with these mutations. In silico analysis predicted that Ser/Arg-rich RNA splicing factor (SRSF) 2 and SRSF5 were the regulatory factors for exon4 and exon5 splicing, respectively. Electrophoretic mobility shift assay confirmed that SRSF2 binds to exon4 and SRSF5 binds to exon5, and mutations in each exon can alter SRSF binding. Transfection of the amelogenin minigene to LS8 ameloblastic cells suppressed expression of the known miR-exon4 direct targets, and , related to multiple pathways. Given the mutations on the minigene, the expression of has been significantly upregulated with c.155C>G and c.155delC mutations. Together, we confirmed that exon4 splicing is critical for miR-exon4 production, and mutations causing X-linked AI in exon4 and exon5 significantly affect exon4 splicing and following miR-exon4 production. The change in miR-exon4 would be an additional etiology of enamel defects seen in some X-linked AI.
Topics: Humans; Amelogenin; Amelogenesis Imperfecta; HEK293 Cells; Mutation; Dental Enamel Proteins; MicroRNAs; RNA, Messenger
PubMed: 37563801
DOI: 10.1177/00220345231180572 -
Advances in Clinical and Experimental... Dec 2022Taurodontism is a morphological anomaly involving multirooted teeth that is characterized by a vertical shift of the pulp chamber and shortening of the roots. The... (Review)
Review
Taurodontism is a morphological anomaly involving multirooted teeth that is characterized by a vertical shift of the pulp chamber and shortening of the roots. The literature was analyzed to determine the impact of a diagnosis of taurodontism on dental treatment. A total of 85 full-text publications from the years 2005-2021 were analyzed and 20 publications were included in this research. The endodontic treatment of a taurodont tooth is challenging due to the apical displacement of the pulpal chamber floor and the incorrect configuration of the root canal system, or the presence of additional canals. In terms of prosthetics, the use of taurodont teeth as abutments is not recommended as they lack stability due to shorter roots. The extraction of taurodont teeth can be complicated due to an apical shift of the root furcation. In periodontology, taurodont teeth can have a better prognosis as there is less chance of furcation involvement. From an orthodontic point of view, it is important to note that taurodont teeth are not sufficiently embedded in the alveolus and have a greater tendency for root resorption. With regard to genetic diseases, it has been reported that this anomaly can exist as an isolated feature. However, the majority of authors agree that taurodontism is associated with conditions such as Down syndrome, Klinefelter syndrome, cleft lip and palate, hypodontia, amelogenesis imperfecta, and others. From a clinical standpoint, it is very important to diagnose taurodontism before treatment. A diagnosis of taurodontism can be important in the early diagnosis of malformations that commonly occur with this condition.
Topics: Humans; Dental Pulp Cavity; Cleft Lip; Cleft Palate; Tooth Abnormalities
PubMed: 36000881
DOI: 10.17219/acem/152120 -
Nature Jul 2020Dental enamel is a principal component of teeth, and has evolved to bear large chewing forces, resist mechanical fatigue and withstand wear over decades. Functional...
Dental enamel is a principal component of teeth, and has evolved to bear large chewing forces, resist mechanical fatigue and withstand wear over decades. Functional impairment and loss of dental enamel, caused by developmental defects or tooth decay (caries), affect health and quality of life, with associated costs to society. Although the past decade has seen progress in our understanding of enamel formation (amelogenesis) and the functional properties of mature enamel, attempts to repair lesions in this material or to synthesize it in vitro have had limited success. This is partly due to the highly hierarchical structure of enamel and additional complexities arising from chemical gradients. Here we show, using atomic-scale quantitative imaging and correlative spectroscopies, that the nanoscale crystallites of hydroxylapatite (Ca(PO)(OH)), which are the fundamental building blocks of enamel, comprise two nanometric layers enriched in magnesium flanking a core rich in sodium, fluoride and carbonate ions; this sandwich core is surrounded by a shell with lower concentration of substitutional defects. A mechanical model based on density functional theory calculations and X-ray diffraction data predicts that residual stresses arise because of the chemical gradients, in agreement with preferential dissolution of the crystallite core in acidic media. Furthermore, stresses may affect the mechanical resilience of enamel. The two additional layers of hierarchy suggest a possible new model for biological control over crystal growth during amelogenesis, and hint at implications for the preservation of biomarkers during tooth development.
Topics: Acids; Amelogenesis; Calcium; Carbonates; Crystallization; Density Functional Theory; Dental Enamel; Durapatite; Fluorides; Humans; Magnesium; Microscopy, Electron, Scanning Transmission; Sodium; Tomography; X-Ray Diffraction
PubMed: 32612224
DOI: 10.1038/s41586-020-2433-3 -
Journal of Dental Research Jan 2022Amelogenesis imperfecta (AI) is an innate disorder that affects the formation and mineralization of the tooth enamel. When diagnosed with AI, one's teeth can be...
Amelogenesis imperfecta (AI) is an innate disorder that affects the formation and mineralization of the tooth enamel. When diagnosed with AI, one's teeth can be hypoplastic (thin enamel), hypomature (normal enamel thickness but discolored and softer than normal enamel), hypocalcified (normal enamel thickness but extremely weak), or mixed conditions of the above. Numerous studies have revealed the genes that are involved in causing AI. Recently, (acid phosphatase 4) was newly found as a gene causing hypoplastic AI, and it was suggested that mutant forms of ACP4 might affect access to the catalytic core or the ability to form a homodimer. In this study, a Korean and a Turkish family with hypoplastic AI were recruited, and their exome sequences were analyzed. Biallelic mutations were revealed in : paternal (NM_033068: c.419C>T, p.(Pro140Leu)) and maternal (c.262C>A, p.(Arg88Ser)) mutations in family 1 and a paternal (c.713C>T, p.(Ser238Leu)) mutation and de novo (c.350A>G, p.(Gln117Arg)) mutation in the maternal allele in family 2. Mutations were analyzed by cloning, mutagenesis, immunofluorescence, immunoprecipitation, and acid phosphatase activity test. Comparison between the wild-type and mutant ACP4s showed a decreased amount of protein expression from the mutant forms, a decreased ability to form a homodimer, and a decreased acid phosphatase activity level. We believe that these findings will not only expand the mutational spectrum of but also increase our understanding of the mechanism of ACP4 function during normal and pathologic amelogenesis.
Topics: Acid Phosphatase; Amelogenesis Imperfecta; Dental Enamel; Humans; Mutation; Pedigree; Tooth
PubMed: 34036831
DOI: 10.1177/00220345211015119 -
Frontiers in Physiology 2023Amelogenesis imperfecta (AI) is a heterogeneous group of genetic rare diseases disrupting enamel development (Smith et al., Front Physiol, 2017a, 8, 333). The clinical...
Amelogenesis imperfecta (AI) is a heterogeneous group of genetic rare diseases disrupting enamel development (Smith et al., Front Physiol, 2017a, 8, 333). The clinical enamel phenotypes can be described as hypoplastic, hypomineralized or hypomature and serve as a basis, together with the mode of inheritance, to Witkop's classification (Witkop, J Oral Pathol, 1988, 17, 547-553). AI can be described in isolation or associated with others symptoms in syndromes. Its occurrence was estimated to range from 1/700 to 1/14,000. More than 70 genes have currently been identified as causative. We analyzed using next-generation sequencing (NGS) a heterogeneous cohort of AI patients in order to determine the molecular etiology of AI and to improve diagnosis and disease management. Individuals presenting with so called "isolated" or syndromic AI were enrolled and examined at the Reference Centre for Rare Oral and Dental Diseases (O-Rares) using D4/phenodent protocol (www.phenodent.org). Families gave written informed consents for both phenotyping and molecular analysis and diagnosis using a dedicated NGS panel named GenoDENT. This panel explores currently simultaneously 567 genes. The study is registered under NCT01746121 and NCT02397824 (https://clinicaltrials.gov/). GenoDENT obtained a 60% diagnostic rate. We reported genetics results for 221 persons divided between 115 AI index cases and their 106 associated relatives from a total of 111 families. From this index cohort, 73% were diagnosed with non-syndromic amelogenesis imperfecta and 27% with syndromic amelogenesis imperfecta. Each individual was classified according to the AI phenotype. Type I hypoplastic AI represented 61 individuals (53%), Type II hypomature AI affected 31 individuals (27%), Type III hypomineralized AI was diagnosed in 18 individuals (16%) and Type IV hypoplastic-hypomature AI with taurodontism concerned 5 individuals (4%). We validated the genetic diagnosis, with class 4 (likely pathogenic) or class 5 (pathogenic) variants, for 81% of the cohort, and identified candidate variants (variant of uncertain significance or VUS) for 19% of index cases. Among the 151 sequenced variants, 47 are newly reported and classified as class 4 or 5. The most frequently discovered genotypes were associated with and for isolated AI. and genes were the most frequent genes identified for syndromic AI. Patients negative to the panel were resolved with exome sequencing elucidating for example the gene involved ie or digenic inheritance. NGS GenoDENT panel is a validated and cost-efficient technique offering new perspectives to understand underlying molecular mechanisms of AI. Discovering variants in genes involved in syndromic AI ( ) transformed patient overall care. Unravelling the genetic basis of AI sheds light on Witkop's AI classification.
PubMed: 37228816
DOI: 10.3389/fphys.2023.1130175 -
Revista Cientifica Odontologica... 2023The main origin of amelogenesis imperfecta (AI) is a genetic alteration inherited by a family member which affects the dental enamel of the teeth of a person with this...
The main origin of amelogenesis imperfecta (AI) is a genetic alteration inherited by a family member which affects the dental enamel of the teeth of a person with this condition in various ways. The present clinical case from the Teaching Dental Clinic of the Peruvian University Cayetano Heredia is of a 6-year 5-month-old male child who came to the dental office accompanied by his father and 8-year-old sister, diagnosed with the same AI condition. The comprehensive treatment proposed for this patient was determined by radiographic and clinical examinations and consultations with specialists in different areas. The purpose of this publication was to report a case and describe possible clinical approaches.
PubMed: 38288452
DOI: 10.21142/2523-2754-1102-2023-156 -
International Journal of Oral Science May 2021Circadian rhythm is involved in the development and diseases of many tissues. However, as an essential environmental regulating factor, its effect on amelogenesis has...
Circadian rhythm is involved in the development and diseases of many tissues. However, as an essential environmental regulating factor, its effect on amelogenesis has not been fully elucidated. The present study aims to investigate the correlation between circadian rhythm and ameloblast differentiation and to explore the mechanism by which circadian genes regulate ameloblast differentiation. Circadian disruption models were constructed in mice for in vivo experiments. An ameloblast-lineage cell (ALC) line was used for in vitro studies. As essential molecules of the circadian system, Bmal1 and Per2 exhibited circadian expression in ALCs. Circadian disruption mice showed reduced amelogenin (AMELX) expression and enamel matrix secretion and downregulated expression of BMAL1, PER2, PPARγ, phosphorylated AKT1 and β-catenin, cytokeratin-14 and F-actin in ameloblasts. According to previous findings and our study, BMAL1 positively regulated PER2. Therefore, the present study focused on PER2-mediated ameloblast differentiation and enamel formation. Per2 knockdown decreased the expression of AMELX, PPARγ, phosphorylated AKT1 and β-catenin, promoted nuclear β-catenin accumulation, inhibited mineralization and altered the subcellular localization of E-cadherin in ALCs. Overexpression of PPARγ partially reversed the above results in Per2-knockdown ALCs. Furthermore, in in vivo experiments, the length of incisor eruption was significantly decreased in the circadian disturbance group compared to that in the control group, which was rescued by using a PPARγ agonist in circadian disturbance mice. In conclusion, through regulation of the PPARγ/AKT1/β-catenin signalling axis, PER2 played roles in amelogenin expression, cell junctions and arrangement, enamel matrix secretion and mineralization during ameloblast differentiation, which exert effects on enamel formation.
Topics: Ameloblasts; Amelogenesis; Animals; Cell Differentiation; Mice; PPAR gamma; Period Circadian Proteins; beta Catenin
PubMed: 34011974
DOI: 10.1038/s41368-021-00123-7 -
Journal of Dental Research Dec 2021The nanofibrous nature and its intricate structural organization are the basis for the extraordinary ability of sound enamel to outlive masticatory forces at minimal... (Review)
Review
The nanofibrous nature and its intricate structural organization are the basis for the extraordinary ability of sound enamel to outlive masticatory forces at minimal failure rates. Apatite nanofibers of several hundreds of micrometers to possibly millimeters in length originate during the secretory stage of amelogenesis as 2-nm-thin and 15-nm-wide ribbons that develop and grow in length under the guidance of a dynamic mixture of specialized proteins, the developing enamel matrix (DEM). A critical role in the unidirectional and oriented growth of enamel mineral ribbons has been attributed to amelogenin, the major constituent of the DEM. This review elaborates on recent studies on the ability of ribbon-like assemblies of amelogenin to template the formation of an amorphous calcium phosphate precursor that transforms into apatite mineral ribbons similar to the ones observed in developing enamel. A mechanistic model of the biological processes that drive biomineralization in enamel is presented in the context of a comparative analysis of enamel mouse models and earlier structural data of the DEM emphasizing a regulatory role of the matrix metalloproteinase 20 in mineral deposition and the involvement of a process-directing agent for the templated mineral growth directed by amelogenin nanoribbons.
Topics: Amelogenesis; Amelogenin; Animals; Dental Enamel; Dental Enamel Proteins; Matrix Metalloproteinase 20; Mice; Nanotubes, Carbon
PubMed: 34009057
DOI: 10.1177/00220345211012925