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Oral Diseases Sep 2022To identify the genetic cause of one Chinese family with hypoplastic amelogenesis imperfecta (AI) and explore the relationship between genotype and its phenotype.
OBJECTIVES
To identify the genetic cause of one Chinese family with hypoplastic amelogenesis imperfecta (AI) and explore the relationship between genotype and its phenotype.
MATERIAL AND METHODS
One Chinese family with generalized hypoplastic AI was recruited. One deciduous tooth from the proband was subjected to scanning electron microscopy. Whole-exome sequencing was performed and identified mutation was confirmed by Sanger sequencing. Bioinformatics studies were further conducted to analyze potential deleterious effects of the mutation.
RESULTS
The proband presented a typical hypoplastic AI phenotype whose teeth in deciduous and permanent dentitions showed thin, yellow, and hard enamel surface. The affected enamel in deciduous tooth showed irregular, broken, and collapsing enamel rods with borders of the enamel prisms undulated and structural shapes of prisms irregular. A novel homozygous nonsense mutation in the last exon of the enamelin (ENAM) gene (NM_031889.3; c.2078C>G) was identified in the proband, which was predicted to produce a highly truncated protein (NP_114095.2; p.(Ser693*)). This mutation was also identified in the proband's parents in heterozygous form. Surprisingly, the clinical phenotype of the heterozygous parents varied from a lack of penetrance to mild enamel defects. Additional bioinformatics studies demonstrated that the detected mutation could change the 3D structure of the ENAM protein and severely damaged the function of ENAM.
CONCLUSION
The novel homozygous ENAM mutation resulted in hypoplastic AI in the present study. Our results provide new genetic evidence that mutations involved in ENAM contribute to hypoplastic AI.
Topics: Amelogenesis Imperfecta; Dental Enamel Proteins; Extracellular Matrix Proteins; Humans; Mutation; Pedigree; Proteins
PubMed: 33864320
DOI: 10.1111/odi.13877 -
L' Orthodontie Francaise Dec 2021Amelogenesis imperfecta is a genetic disease, characterized by a structural defect of the enamel and has variable clinical expressions. It can be isolated or associated... (Review)
Review
INTRODUCTION
Amelogenesis imperfecta is a genetic disease, characterized by a structural defect of the enamel and has variable clinical expressions. It can be isolated or associated as part of a syndrome. Three clinical forms exist: hypoplastic, hypomature and hypomineralized.
DISCUSSION
Enamel fragility involves dentin exposure and dental hypersensitivity as frequent consequences. Some severe forms are mainly associated with an anterior open bite. The care of these patients constitutes a real challenge for the dentist. Materials et Methods: A literature review was carried out using the PubMed, Web of Science and Scopus interfaces over the past ten years in order to highlight the different treatment options available.
CONCLUSION
From conservative to surgical treatment, it is necessary to develop a collaboration between the orthodontist and the pediatric dentist in order to offer multidisciplinary care adapted to the patient's needs.
Topics: Amelogenesis Imperfecta; Child; Humans; Open Bite
PubMed: 34911673
DOI: 10.1684/orthodfr.2021.64 -
Journal of Dental Research Apr 2020Amelogenesis imperfecta (AI) is a collection of genetic disorders affecting the quality and/or quantity of tooth enamel. More than 20 genes are, so far, known to be...
Amelogenesis imperfecta (AI) is a collection of genetic disorders affecting the quality and/or quantity of tooth enamel. More than 20 genes are, so far, known to be responsible for this condition. In this study, we recruited 3 Turkish families with hypomaturation AI. Whole-exome sequence analyses identified disease-causing mutations in each proband, and these mutations cosegregated with the AI phenotype in all recruited members of each family. The AI-causing mutations in family 1 were a novel mutation [NM_182680.1:c.143T>C, p.(Leu48Ser)] in the proband and a novel homozygous mutation [NM_004771.3:c.616G>A, p.(Asp206Asn)] in the mother of the proband. Previously reported compound heterozygous mutations [NM_004771.3:c.103A>C, p.(Arg35=) and c.389C>T, p.(Thr130Ile)] caused the AI in family 2 and family 3. Minigene splicing analyses revealed that the missense mutation increased exonic definition of exon 4 and the synonymous mutation decreased exonic definition of exon 1. These mutations would trigger an alteration of exon usage during RNA splicing, causing the enamel malformations. These results broaden our understanding of molecular genetic pathology of tooth enamel formation.
Topics: Amelogenesis Imperfecta; Dental Enamel; Exons; Humans; Mutation; Pedigree
PubMed: 31999931
DOI: 10.1177/0022034520901708 -
Journal of Dental Research Jun 2024Amelogenesis imperfecta (AI) is a diverse group of inherited diseases featured by various presentations of enamel malformations that are caused by disturbances at...
Amelogenesis imperfecta (AI) is a diverse group of inherited diseases featured by various presentations of enamel malformations that are caused by disturbances at different stages of enamel formation. While hypoplastic AI suggests a thickness defect of enamel resulting from aberrations during the secretory stage of amelogenesis, hypomaturation AI indicates a deficiency of enamel mineralization and hardness established at the maturation stage. Mutations in , which encodes the largest enamel matrix protein, enamelin, have been demonstrated to cause generalized or local hypoplastic AI. Here, we characterized 2 AI families with disparate hypoplastic and hypomaturation enamel defects and identified 2 distinct indel mutations at the same location of , c588+1del and c.588+1dup. Minigene splicing assays demonstrated that they caused frameshifts and truncation of ENAM proteins, p.Asn197Ilefs*81 and p.Asn197Glufs*25, respectively. In situ hybridization of on mouse mandibular incisors confirmed its restricted expression in secretory stage ameloblasts and suggested an indirect pathogenic mechanism underlying hypomaturation AI. In silico analyses indicated that these 2 truncated ENAMs might form amyloid structures and cause protein aggregation with themselves and with wild-type protein through the added aberrant region at their C-termini. Consistently, protein secretion assays demonstrated that the truncated proteins cannot be properly secreted and impede secretion of wild-type ENAM. Moreover, compared to the wild-type, overexpression of the mutant proteins significantly increased endoplasmic reticulum stress and upregulated the expression of unfolded protein response (UPR)-related genes and , a UPR-controlled proapoptotic gene. Caspase, terminal deoxynucleotidyl transferase UTP nick-end labeling (TUNEL), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays further revealed that both truncated proteins, especially p.Asn197Ilefs*81, induced cell apoptosis and decreased cell survival, suggesting that the 2 mutations cause AI through ameloblast cell pathology and death rather than through a simple loss of function. This study demonstrates that an mutation can lead to generalized hypomaturation enamel defects and suggests proteinopathy as a potential pathogenesis for -associated AI.
Topics: Amelogenesis Imperfecta; Animals; Mice; Humans; Ameloblasts; Female; Male; Mutation; Dental Enamel Proteins; Pedigree; Apoptosis; In Situ Hybridization; Extracellular Matrix Proteins
PubMed: 38716742
DOI: 10.1177/00220345241236695 -
Frontiers in Genetics 2022Amelogenesis imperfecta is a congenital disorder within a heterogeneous group of conditions characterized by enamel hypoplasia. Patients suffer from early tooth loss,...
Amelogenesis imperfecta is a congenital disorder within a heterogeneous group of conditions characterized by enamel hypoplasia. Patients suffer from early tooth loss, social embarrassment, eating difficulties, and pain due to an abnormally thin, soft, fragile, and discolored enamel with poor aesthetics and functionality. The etiology of amelogenesis imperfecta is complicated by genetic interactions. To identify mouse amelogenesis imperfecta-related genes (mAIGenes) and their respective phenotypes, we conducted a systematic literature review and database search and found and curated 70 mAIGenes across all of the databases. Our pathway enrichment analysis indicated that these genes were enriched in tooth development-associated pathways, forming four distinct groups. To explore how these genes are regulated and affect the phenotype, we predicted microRNA (miRNA)-gene interaction pairs using our bioinformatics pipeline. Our miRNA regulatory network analysis pinpointed that miR-16-5p, miR-27b-3p, and miR-23a/b-3p were hub miRNAs. The function of these hub miRNAs was evaluated through ameloblast differentiation assays with/without the candidate miRNA mimics using cultured mouse ameloblast cells. Our results revealed that overexpression of miR-16-5p and miR-27b-3p, but not miR-23a/b-3p, significantly inhibited ameloblast differentiation through regulation of mAIGenes. Thus, our study shows that miR-16-5p and miR-27b-3p are candidate pathogenic miRNAs for amelogenesis imperfecta.
PubMed: 35401675
DOI: 10.3389/fgene.2022.788259 -
European Archives of Paediatric... Dec 2022Amelogenesis imperfecta (AI) is a hereditary condition which affects the composition and structure of enamel in terms of hypoplasia and/or hypomineralization. The...
PURPOSE
Amelogenesis imperfecta (AI) is a hereditary condition which affects the composition and structure of enamel in terms of hypoplasia and/or hypomineralization. The condition severely affects patients facing such difficulties as hypersensibility, loss of tooth substance and poor aesthetics. The objective is to perform a systematic review of patient-reported outcome measures (PROMs) in patients with amelogenesis imperfecta.
METHODS
Inclusion criteria were articles written in English, including PROMs from patients with amelogenesis imperfecta. The databases PubMed, Scopus and Web of Science were searched on April 27, 2022, and eligible articles were screened. Exclusion criteria were articles based on proxy reports and single case reports.
RESULTS
405 studies were screened in terms of title and abstract, with 31 articles eligible for full-text screening, resulting in a total of 11 articles eligible for inclusion, (articles including 4-82 patients). The content was analyzed, resulting in the outcome divided into seven domains: Oral Health-Related Quality of Life (OHRQoL), Dental fear, Esthetics, Psychosocial factors, Function, Dental hypersensitivity, and Treatment outcome.
CONCLUSION
The limited quantity of research on PROMS from patients with AI indicates a significant impact of OHRQoL and daily life. A large variety of approaches have been presented in the articles. Patients report concerns of esthetics, hypersensitivity, function, and a general impact on well-being and social interaction. This highlights the importance for the need of early dental treatment.
PROSPERO REGISTRATION NUMBER
256875.
Topics: Humans; Amelogenesis Imperfecta; Quality of Life; Dental Enamel; Patient Reported Outcome Measures
PubMed: 35896941
DOI: 10.1007/s40368-022-00737-3 -
Journal of Applied Oral Science :... 2020Gingival conditions and tooth sensitivity of young patients with amelogenesis imperfecta lack in depth studies. This case-control study aimed to compare (1) the gingival...
METHODOLOGY
Gingival conditions and tooth sensitivity of young patients with amelogenesis imperfecta lack in depth studies. This case-control study aimed to compare (1) the gingival inflammation, the presence of enamel defects, and tooth sensitivity in young patients with and without amelogenesis imperfecta and (2) to investigate if any difference exists between subtypes of amelogenesis imperfecta. We compared forty-two participants with amelogenesis imperfecta with forty-two controls matched for age, gender, and the number of examined sites. Based on interview, clinical examination, and intraoral photography, we collected data on periodontal conditions, enamel defects and the presence of tooth sensitivity. Comparison tests were performed to investigate if any difference existed between cases and controls; and among cases, between the different subtypes of amelogenesis imperfecta. We performed a post-hoc analysis for any significant difference observed.
RESULTS
We observed more gingival inflammation, enamel defects and tooth sensitivity among cases (all p<0.05). Participants with hypocalcified amelogenesis imperfecta had more gingival inflammation, enamel defects, and tooth sensitivity than patients with the hypoplastic and hypomature subtypes (all p<0.05). After adjustment for dental plaque, gingival inflammation was associated with the presence of amelogenesis imperfecta (OR (95%CI) = 1.14 (1.05; 1.24). p<0.01).
CONCLUSION
Gingival inflammation, enamel defect and tooth sensitivity are more frequently observed among young patients with amelogenesis imperfecta, and more specifically among children with the hypocalcified subtype.
Topics: Amelogenesis Imperfecta; Case-Control Studies; Child; Dental Enamel; Dentin Sensitivity; Female; Humans; Inflammation; Male
PubMed: 32997085
DOI: 10.1590/1678-7757-2020-0170 -
International Journal of Clinical... Jul 2021Amelogenesis imperfecta and generalised enamel hypoplasia are developmental dental anomalies that affect dental enamel. While amelogenesis imperfecta results from...
AIMS
Amelogenesis imperfecta and generalised enamel hypoplasia are developmental dental anomalies that affect dental enamel. While amelogenesis imperfecta results from various gene mutations, the exact underlying mechanisms of the etiopathogenesis of both remain unclear. This study aims to evaluate Ghrelin hormone levels in children with generalised enamel hypoplasia to establish whether Ghrelin might have a potential role in enamel hypoplasia's etiology. The second purpose is to determine the correlations among the blood levels of Ghrelin, growth hormone (GH), insulin-like growth factor-1 (IGF-1), bone alkaline phosphatase (BALP) and osteocalcin (OC) that are vital in dental development.
MATERIAL AND METHODS
Study was designed with two study groups, AI (hypoplastic amelogenesis imperfecta) (n = 15; mean-age 10.36 ± 1.90) and GEH (idiopathic generalised enamel hypoplasia) (n = 15; mean-age 10.42 ± 1.84), and a healthy control (n = 15; mean-age 10.39 ± 1.91) group. After fasting for 10-12 hours, simultaneous blood samples were collected; then, after centrifugation, serum and plasma were stored at -80°C until the day of analysis. Total Ghrelin levels of plasma and serum levels of GH, IGF-1, BALP and OC were measured using commercial ELISA kits.
RESULTS
Ghrelin levels of AI and GEH groups were significantly lower (P < .01) than the control group.
CONCLUSION
This is the first study to reveal the decreased levels of Ghrelin in plasma of children with generalised enamel hypoplasia, suggesting a potential role for Ghrelin in amelogenesis. In order to determine its function in enamel formation, further studies should be carried out. The result of the present study suggests that paediatricians refer children with abnormal Ghrelin levels to a paediatric dentist to contribute to appropriate prophylactic and therapeutic interventions. Generalised enamel hypoplasia may also indicate possible abnormalities in Ghrelin levels for paediatricians. Therefore, paediatricians' knowledge about the clinical appearance of generalised enamel hypoplasia should be increased.
Topics: Amelogenesis; Amelogenesis Imperfecta; Child; Ghrelin; Humans; Mutation
PubMed: 33871148
DOI: 10.1111/ijcp.14223 -
Head & Face Medicine Jun 2024Amelogenesis imperfecta (AI) is a genetically determined, non-syndromic enamel dysplasia that may manifest as hypoplasia, hypomaturation, or hypocalcification and can...
INTRODUCTION
Amelogenesis imperfecta (AI) is a genetically determined, non-syndromic enamel dysplasia that may manifest as hypoplasia, hypomaturation, or hypocalcification and can commonly be classified into four primary groups. In this retrospective analysis, specific orofacial characteristics are described and associated with each of the AI types based on a patient cohort from Witten/Herdecke University, Germany.
METHODS
Data from 19 patients (ten male and nine female, mean age 12.27 ± 4.06 years) with AI who presented at the Department of Orthodontics between July 2011 and December 2023 were analyzed. Baseline skeletal and dental conditions were assessed, including the presence of hypodontia, displacements, and taurodontism. AI was classified into classes I-IV based on phenotype. Treatment needs were evaluated according to the main findings following the German KIG classification, while the radiological enamel situation was determined using panoramic radiographs.
RESULTS
An approximately equal distribution between classes II and III was found and a slight inclination toward a dolichofacial configuration (ΔML-NSL: 5.07 ± 9.23°, ΔML-NL: 4.24 ± 8.04°). Regarding orthodontic findings, disturbance in tooth eruption as well as open bite were the most prevalent issues (both 36.8%, n = 7). The most common AI classes were type I and II, which show an almost even distribution about the skeletal classes in sagittal dimension, while dolichofacial configuration was found most frequently in vertical dimension.
CONCLUSION
Both clinical and radiological orthodontic findings in context with AI are subject to extensive distribution. It seems that no specific orofacial findings can be confirmed in association with AI with regard to the common simple classes I-IV. It may be more appropriate to differentiate the many subtypes according to their genetic aspects to identify possible associated orthodontic findings.
Topics: Humans; Amelogenesis Imperfecta; Male; Female; Retrospective Studies; Child; Adolescent; Germany; Radiography, Panoramic; Orthodontics, Corrective; Malocclusion
PubMed: 38877506
DOI: 10.1186/s13005-024-00436-y -
Gaceta Medica de Mexico 2019Amelogenesis imperfecta is a group of developmental disorders of the dental enamel that is mainly associated with mutations in the AMELX gene. Clinically, it presents... (Review)
Review
Amelogenesis imperfecta is a group of developmental disorders of the dental enamel that is mainly associated with mutations in the AMELX gene. Clinically, it presents different phenotypes that affect the structure and function of dental enamel both in primary and secondary dentition. The purpose of this study was to conduct a literature review on the AMELX functions and mutations that are related to amelogenesis imperfecta. A literature search was carried out in two databases: PubMed and Web of Science, using the keywords "AMELX", "amelogenin", "amelogenesis imperfecta" and "AMELX mutation". Forty articles were reviewed, with AMELX being found to be the predominant gene in the development of dental enamel and amelogenesis imperfecta by altering the structure of amelogenin. In the past few years, the characteristics of the amelogenesis imperfecta process have been described with different phenotypes of hypoplastic or hypo-mineralized enamel, and different mutations have been reported, by means of which the gene sequencing and the position of mutations have been determined.
Topics: Amelogenesis Imperfecta; Amelogenin; Dental Enamel; Humans; Mutation; Phenotype
PubMed: 30799455
DOI: 10.24875/GMM.18003604