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Pediatric Nephrology (Berlin, Germany) Aug 2023
Topics: Humans; Nephrocalcinosis; Syndrome; Amelogenesis Imperfecta
PubMed: 36917294
DOI: 10.1007/s00467-023-05904-2 -
Pediatric Nephrology (Berlin, Germany) Aug 2023
Topics: Humans; Nephrocalcinosis; Mutation
PubMed: 36917292
DOI: 10.1007/s00467-023-05908-y -
Journal of Dental Research Jan 2024Amelogenesis imperfecta (AI) comprises a group of rare, inherited disorders with abnormal enamel formation. Ameloblastin (AMBN), the second most abundant enamel matrix...
Amelogenesis imperfecta (AI) comprises a group of rare, inherited disorders with abnormal enamel formation. Ameloblastin (AMBN), the second most abundant enamel matrix protein (EMP), plays a critical role in amelogenesis. Pathogenic biallelic loss-of-function variants are known to cause recessive hypoplastic AI. A report of a family with dominant hypoplastic AI attributed to AMBN missense change p.Pro357Ser, together with data from animal models, suggests that the consequences of variants in human AI remain incompletely characterized. Here we describe 5 new pathogenic variants in 11 individuals with AI. These fall within 3 groups by phenotype. Group 1, consisting of 6 families biallelic for combinations of 4 different variants, have yellow hypoplastic AI with poor-quality enamel, consistent with previous reports. Group 2, with 2 families, appears monoallelic for a variant shared with group 1 and has hypomaturation AI of near-normal enamel volume with pitting. Group 3 includes 3 families, all monoallelic for a fifth variant, which are affected by white hypoplastic AI with a thin intact enamel layer. Three variants, c.209C>G; p.(Ser70*) (groups 1 and 2), c.295T>C; p.(Tyr99His) (group 1), and c.76G>A; p.(Ala26Thr) (group 3) were identified in multiple families. Long-read locus sequencing revealed these variants are on the same conserved haplotype, implying they originate from a common ancestor. Data presented therefore provide further support for possible dominant as well as recessive inheritance for -related AI and for multiple contrasting phenotypes. In conclusion, our findings suggest pathogenic variants have a more complex impact on human AI than previously reported.
Topics: Animals; Humans; Amelogenesis; Amelogenesis Imperfecta; Dental Enamel Proteins; Pedigree; Phenotype
PubMed: 38058155
DOI: 10.1177/00220345231203694 -
Journal of Esthetic and Restorative... Jun 2024The aim of this review was to compare various types of restorations used in children and young adults affected with amelogenesis imperfecta (AI) to determine the most... (Review)
Review
OBJECTIVE
The aim of this review was to compare various types of restorations used in children and young adults affected with amelogenesis imperfecta (AI) to determine the most effective restorative treatment.
METHODS
This systematic review included randomized controlled trials, retrospective and prospective cohorts conducted on children and young adults diagnosed with amelogenesis imperfecta and written in French or English. A systematic search was conducted using four databases, namely Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via PubMed, Science Direct and Scopus, using a selection of MeSH terms: "Amelogenesis Imperfecta," "Therapeutics," "Treatment Outcome," "Adult, young," "Child," "Dental Restoration, Permanent," "Dental Restoration, Temporary," and "Esthetics, Dental."
RESULTS
Out of 138 articles identified in the initial search, four articles met all the inclusion criteria. The results showed that ceramic restorations had better quality scores and longevity compared to other restorations.
CONCLUSION
Ceramic restorations could be considered the restorative treatment modality of choice for AI-affected children and young adults. However, more high-quality clinical trials involving young patients affected with AI are required to evaluate and compare the outcomes of different restorative approaches.
CLINICAL SIGNIFICANCE
Young patients affected with amelogenesis imperfecta usually suffer from low self-esteem, psychological problems and social avoidance, caused by the alteration of teeth such as discoloration, sensitivity, fractures and reduced size. For the dentist, selecting the appropriate restorative treatment for AI in young patients could be a veritable challenge. Therefore, it is important to have an evidence-based modality. For this reason, in this review, the different restorative approaches used in AI-affected young patients were compared to recommend the most effective treatment.
Topics: Humans; Amelogenesis Imperfecta; Child; Dental Restoration, Permanent; Young Adult; Adolescent
PubMed: 38258433
DOI: 10.1111/jerd.13191 -
Special Care in Dentistry : Official... 2024Amelogenesis Imperfecta (AI) is a disorder of tooth development characterized by abnormal enamel formation. In order to detect other dental and jawbone abnormalities... (Comparative Study)
Comparative Study
BACKGROUND
Amelogenesis Imperfecta (AI) is a disorder of tooth development characterized by abnormal enamel formation. In order to detect other dental and jawbone abnormalities that could be associated with AI, a retrospective and analytic study was conducted comparing panoramic radiographs of AI and non-AI patients.
MATERIAL AND METHODS
Digital panoramic radiographs of 60 AI and 60 non-AI patients were examined. Abnormalities in dental number, size, shape, eruption, and in the shape of the dental arches were checked and blindly recorded by two experimented observers. Descriptive statistics using percentages and chi-square test with .05 level of significance value was used.
RESULTS
Prevalence of supernumerary teeth, dental agenesis, microdontia, taurodontism, radicular dilacerations, dental inclusions, temporary teeth persistence, and pulp calcifications was significantly higher in AI patients compared to control patients. Prevalence of periapical images, cysts, and hypercementosis was lower in AI patients compared to control patients, with no statistically significant difference. A significant prevalence of mandibular hypoplasia was also noted in AI patients.
CONCLUSION
In addition to enamel defect, panoramic radiography was useful in detecting other dental abnormalities and mandibular hypoplasia associated with AI and should therefore be systematically indicated for AI patients' care.
Topics: Humans; Amelogenesis Imperfecta; Radiography, Panoramic; Retrospective Studies; Female; Male; Tooth Abnormalities; Adolescent; Child; Adult; Prevalence
PubMed: 37885117
DOI: 10.1111/scd.12935 -
Journal of Esthetic and Restorative... Jul 2023This article will provide an overview of the clinical presentation, treatment considerations, and sequencing of treatment for a patient with amelogenesis imperfecta...
OBJECTIVES
This article will provide an overview of the clinical presentation, treatment considerations, and sequencing of treatment for a patient with amelogenesis imperfecta (AI). The different types and subgroups of AI will be described, focusing on Type I hypoplastic form of the condition.
OVERVIEW
Patients with AI all have abnormal enamel formation but some may also present with vertical dysgnathia, anterior open bite, and posterior crossbite. A case report demonstrates the sequencing and implementation of necessary orthodontic and prosthodontic treatments, beginning in the mixed dentition and ending with esthetic and functional permanent restorations in the permanent dentition.
CLINICAL SIGNIFICANCE
AI is a disorder of tooth enamel formation but may also affect the face, jaw relationship, occlusion, compromised esthetics, and can potentially cause psychological damage due to the appearance of the teeth. Treatment of AI should be initiated at a young age.
Topics: Humans; Amelogenesis Imperfecta; Dental Enamel; Tooth; Malocclusion
PubMed: 37158443
DOI: 10.1111/jerd.13063 -
International Endodontic Journal Aug 2023Biallelic loss-of-function FAM20A mutations cause amelogenesis imperfecta (AI) type IG, better known as enamel renal syndrome (ERS), characterized by severe enamel...
AIM
Biallelic loss-of-function FAM20A mutations cause amelogenesis imperfecta (AI) type IG, better known as enamel renal syndrome (ERS), characterized by severe enamel hypoplasia, delayed/failed tooth eruption, intrapulpal calcifications, gingival hyperplasia and nephrocalcinosis. FAM20A binds to FAM20C, the Golgi casein kinase (GCK) and potentiates its function to phosphorylate secreted proteins critical for biomineralization. While many FAM20A pathogenic mutations have been reported, the pathogeneses of orodental anomalies in ERS remain to be elucidated. This study aimed to identify disease-causing mutations for patients with ERS phenotypes and to discern the molecular mechanism underlying ERS intrapulpal calcifications.
METHODOLOGY
Phenotypic characterization and whole exome analyses were conducted for 8 families and 2 sporadic cases with hypoplastic AI. A minigene assay was performed to investigate the molecular consequences of a FAM20A splice-site variant. RNA sequencing followed by transcription profiling and gene ontology (GO) analyses were carried out for dental pulp tissues of ERS and the control.
RESULTS
Biallelic FAM20A mutations were demonstrated for each affected individual, including 7 novel pathogenic variants: c.590-5T>A, c.625T>A (p.Cys209Ser), c.771del (p.Gln258Argfs*28), c.832_835delinsTGTCCGACGGTGTCCGACGGTGTC CA (p.Val278Cysfs*29), c.1232G>A (p.Arg411Gln), c.1297A>G (p.Arg433Gly) and c.1351del (p.Gln451Serfs*4). The c.590-5T>A splice-site mutation caused Exon 3 skipping, which resulted in an in-frame deletion of a unique region of the FAM20A protein, p.(Asp197_Ile214delinsVal). Analyses of differentially expressed genes in ERS pulp tissues demonstrated that genes involved in biomineralization, particularly dentinogenesis, were significantly upregulated, such as DSPP, MMP9, MMP20 and WNT10A. Enrichment analyses indicated overrepresentation of gene sets associated with BMP and SMAD signalling pathways. In contrast, GO terms related to inflammation and axon development were underrepresented. Among BMP signalling genes, BMP agonists GDF7, GDF15, BMP3, BMP8A, BMP8B, BMP4 and BMP6 were upregulated, while BMP antagonists GREM1, BMPER and VWC2 showed decreased expression in ERS dental pulp tissues.
CONCLUSIONS
Upregulation of BMP signalling underlies intrapulpal calcifications in ERS. FAM20A plays an essential role in pulp tissue homeostasis and prevention of ectopic mineralization in soft tissues. This critical function probably depends upon MGP (matrix Gla protein), a potent mineralization inhibitor that must be properly phosphorylated by FAM20A-FAM20C kinase complex.
Topics: Humans; Nephrocalcinosis; Amelogenesis Imperfecta; Dental Pulp; Dental Enamel Proteins; Mutation; Calcinosis; Gene Expression Profiling; Carrier Proteins
PubMed: 37159186
DOI: 10.1111/iej.13928 -
Bone Jul 2023Truncation mutations in FAM83H are the major cause of autosomal dominant hypocalcified amelogenesis imperfecta. Some studies also indicated that FAM83H could be involved...
Truncation mutations in FAM83H are the major cause of autosomal dominant hypocalcified amelogenesis imperfecta. Some studies also indicated that FAM83H could be involved in osteogenic differentiation; however, the function of FAM83H in bone formation was rarely explored. This study aimed to explore the effect of Fam83h mutation on skeletal development. We generated Fam83h c.1186C>T (p.Q396*) knockin C57/BL6J mice by CRISPR/Cas9 technology and found that the Fam83h male mice presented skeletal development retardation that was inconspicuous at birth but progressively worsened as they grew up. Alcian and Alizarin Red staining of the whole-mount skeleton showed Fam83h mice presented obvious skeletal development retardation. Moreover, Micro-computed tomography (Micro-CT) analysis and H&E staining showed that the mandible of Fam83h mice exhibited decreased bone trabecula and slight bone rarefaction compared with wild-type mice. Calcium and phosphorus content of serum and bone, and serum ALP activity analysis showed that the serum ALP activity and value of bone calcium were decreased in Fam83h mice. The reduced expression of mineralization markers of RUNX2, OSX, OCN, and COL1, the reduced ALP activity and the weakened ARS staining exhibited in osteoblasts isolated from 3-day-old Fam83h mice. The increased protein expression of casein kinase 1α (CK1α) in the cytoplasm and the decreased expression of β-CATENIN in the nucleus indicated the inhibiting Wnt/β-catenin signaling in osteoblasts from Fam83h mice. Furthermore, agonists of Wnt/β-catenin signaling and Ck1α siRNA partially reversed the mineralization inhibition and the decreased expression of key signaling molecules in osteoblasts of Fam83h mice. In conclusion, Fam83h mutation caused the increase of cytoplasmic CK1α (as one of the components of the degradation complex), which in turn promoted degradation of β-CATENIN in the cytoplasm and reduced β-CATENIN translocation into the nucleus, subsequently inhibited Wnt/β-catenin signaling in osteoblast differentiation, and thus resulted in the mandible underdevelopment in Fam83h male mice.
Topics: Mice; Male; Animals; Osteogenesis; beta Catenin; Calcium; X-Ray Microtomography; Mutation; Osteoblasts; Wnt Signaling Pathway; Mandible; Cell Differentiation
PubMed: 37028581
DOI: 10.1016/j.bone.2023.116756 -
International Journal of Paleopathology Sep 2023Molar incisor hypomineralisation (MIH) is a developmental defect of enamel affecting the first permanent molars and often the incisors and affecting approximately 13% of... (Review)
Review
OBJECTIVE
Molar incisor hypomineralisation (MIH) is a developmental defect of enamel affecting the first permanent molars and often the incisors and affecting approximately 13% of the current population worldwide. Here, we aim to highlight potential differential diagnoses of MIH in archaeological collections (taphonomic discoloration, amelogenesis imperfecta, fluorosis, rachitic teeth, etc.).
METHODS
Causative factors of dental discolourations are identified through a literature review.
RESULTS
In an archaeological context, the sediments contained in the burial soil can lead to tooth discoloration. Taphonomic staining of the dentition may have a similar appearance to enamel hypomineralisation, and thus is a confounding factor that has the potential to cause miscalculation of the true prevalence of MIH within archaeological collections. Some rare medieval cases are reported in the modern literature but without microanalysis, misdiagnosis is possible. The aetiological factors of MIH are unknown but probably follow the multifactorial model involving systemic medical and genetic factors.
CONCLUSIONS
Systematic detection and diagnosis of MIH during anthropological studies is therefore of great interest.
SIGNIFICANCE
The hypotheses that only contemporary agents are causative factors of MIH could be refuted by the discovery of individuals living before medication or pollutants. The identification of MIH in a group of individuals also provides information regarding the health status of a population and reflects stress occurring during the period of mineralisation of the first permanent molars after secretion of the enamel matrix.
LIMITATIONS
Taphonomic alterations of archaeological remains prevent MIH diagnosis.
SUGGESTIONS FOR FUTURE RESEARCH
MIH diagnosis can be difficult in archaeological series and further non-destructive methods (microtomography, elemental analyses, etc.) are required.
Topics: Humans; Molar Hypomineralization; Molar; Incisor; Tooth Demineralization; Prevalence
PubMed: 37523814
DOI: 10.1016/j.ijpp.2023.07.004 -
Journal of Personalized Medicine Oct 2023Hereditary conditions that affect tooth enamel in quantity and/or quality are called amelogenesis imperfecta (AI). AI can occur as an isolated condition or as a symptom...
Hereditary conditions that affect tooth enamel in quantity and/or quality are called amelogenesis imperfecta (AI). AI can occur as an isolated condition or as a symptom of a syndrome. An OMIM search with the term "AI" yielded 79 result entries. Mutations in the same gene cause syndromic or non-syndromic AI, depending on the nature of the mutations. In this study, we recruited two AI families and performed mutational analysis using whole-exome sequencing. The proband of family 1, with hypoplastic pitted AI and mild localized atopic dermatitis, had compound heterozygous mutations (paternal NM_000494.4: c.3598G>T, p.Asp1200Tyr and maternal c.1700G>A, p.Gly567Glu). The proband of family 2, with hypoplastic pitted AI and Jervell and Lange-Nielsen syndrome, had a recurrent mutation (NM_000228.3: c.3463_3475del, p.(Glu1155Thrfs*51)) in addition to compound heterozygous mutations in the KCNQ1 gene.
PubMed: 37888105
DOI: 10.3390/jpm13101494