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Clinical and Experimental Dental... Feb 2020The aim of this retrospective study was to evaluate clinical success and satisfaction of patients with amelogenesis imperfecta treated with three different types of...
OBJECTIVE
The aim of this retrospective study was to evaluate clinical success and satisfaction of patients with amelogenesis imperfecta treated with three different types of bonded restorations at a university clinic.
MATERIALS AND METHODS
One hundred fifty-four restorations in 15 subjects with mean age of 17.3 years (SD 8.2) were evaluated after treatment with three different types of bonded restorations: all ceramic enamel-dentin bonded restorations, prefabricated composite veneers, and direct composite resin restorations. A modified version of the Californian Dental Association system for quality evaluation of dental care and a questionnaire assessing patient satisfaction were used for classification. The restorations were evaluated with respect to patient satisfaction, esthetics, technical, and biological complications.
RESULTS
Mean observation period for the restorations was 42.5 months (SD 35.6). All restorations were in place at the time of the examination. Surface and color calibration showed a success of 95% for the ceramic enamel-dentin bonded restorations, 44% for the direct composite resin restorations, and 0% for the prefabricated composite veneers. The same pattern was evident for anatomy and marginal integrity. The subjects reported a high degree of satisfaction with both the esthetics and function of their restorations.
CONCLUSION
The results indicated that all ceramic restorations demonstrated the best results for patients with amelogenesis imperfecta.
Topics: Adolescent; Adult; Amelogenesis Imperfecta; Ceramics; Child; Child, Preschool; Composite Resins; Dental Restoration Repair; Dental Veneers; Esthetics, Dental; Female; Follow-Up Studies; Humans; Male; Patient Satisfaction; Resin Cements; Retrospective Studies; Treatment Outcome; Young Adult
PubMed: 32067400
DOI: 10.1002/cre2.243 -
Scientific Reports Jan 2021Mutations of Odontogenesis-Associated Phosphoprotein (ODAPH, OMIM *614829) cause autosomal recessive amelogenesis imperfecta, however, the function of ODAPH during...
Mutations of Odontogenesis-Associated Phosphoprotein (ODAPH, OMIM *614829) cause autosomal recessive amelogenesis imperfecta, however, the function of ODAPH during amelogenesis is unknown. Here we characterized normal Odaph expression by in situ hybridization, generated Odaph truncation mice using CRISPR/Cas9 to replace the TGC codon encoding Cys41 into a TGA translation termination codon, and characterized and compared molar and incisor tooth formation in Odaph, Odaph, and Odaph mice. We also searched genomes to determine when Odaph first appeared phylogenetically. We determined that tooth development in Odaph and Odaph mice was indistinguishable in all respects, so the condition in mice is inherited in a recessive pattern, as it is in humans. Odaph is specifically expressed by ameloblasts starting with the onset of post-secretory transition and continues until mid-maturation. Based upon histological and ultrastructural analyses, we determined that the secretory stage of amelogenesis is not affected in Odaph mice. The enamel layer achieves a normal shape and contour, normal thickness, and normal rod decussation. The fundamental problem in Odaph mice starts during post-secretory transition, which fails to generate maturation stage ameloblasts. At the onset of what should be enamel maturation, a cyst forms that separates flattened ameloblasts from the enamel surface. The maturation stage fails completely.
Topics: Ameloblasts; Amelogenesis; Amelogenesis Imperfecta; Animals; Dental Enamel; Extracellular Matrix Proteins; Gene Knock-In Techniques; In Situ Hybridization; Incisor; Mice; Molar; Odontogenesis; Phosphoproteins
PubMed: 33441959
DOI: 10.1038/s41598-020-80912-y -
Frontiers in Physiology 2022Enamel Renal Syndrome (ERS) is a rare genetic disorder caused by biallelic mutations in Family with sequence similarity 20A () gene encoding the secretory pathway...
Enamel Renal Syndrome (ERS) is a rare genetic disorder caused by biallelic mutations in Family with sequence similarity 20A () gene encoding the secretory pathway pseudokinase FAM20A. ERS is characterized by hypoplastic amelogenesis imperfecta (AI), impaired tooth eruption, intra-pulpal calcifications, gingival fibromatosis and nephrocalcinosis of various severity. Previous studies showed that the hypoplastic enamel was also hypomineralized but its chemical composition has not been extensively studied. Furthermore it is currently unclear whether dentinal defects are associated with AI in ERS patients. The objective of the study was to provide a structural and chemical analysis of enamel, dentin and dentin enamel junction (DEJ) in ERS patients carrying four, previously reported, distinct mutations in FAM20A. Chemical cartography obtained with Raman microscopy showed that compared to control samples, ERS enamel composition was severely altered and a cementum-like structure was observed in some cases. Chemical composition of peripulpal dentin was also affected and usual gradient of phosphate intensity, shown in DEJ profile, was absent in ERS samples. DEJ and dentinal anomalies were further confirmed by scanning electron microscopy analysis. In conclusion, our study shows that enamel formation is severely compromised in ERS patients and provides evidence that dentinal defects are an additional feature of the ERS dental phenotype.
PubMed: 36091358
DOI: 10.3389/fphys.2022.957110 -
Frontiers in Endocrinology 2021The enamel renal syndrome (ERS) is a rare disorder featured by amelogenesis , gingival fibromatosis and nephrocalcinosis. ERS is caused by bi-allelic mutations in the...
The enamel renal syndrome (ERS) is a rare disorder featured by amelogenesis , gingival fibromatosis and nephrocalcinosis. ERS is caused by bi-allelic mutations in the secretory pathway pseudokinase FAM20A. How mutations in may modify the gingival connective tissue homeostasis and cause fibromatosis is currently unknown. We here analyzed conditioned media of gingival fibroblasts (GFs) obtained from four unrelated ERS patients carrying distinct mutations and control subjects. Secretomic analysis identified 109 dysregulated proteins whose abundance had increased (69 proteins) or decreased (40 proteins) at least 1.5-fold compared to control GFs. Proteins over-represented were mainly involved in extracellular matrix organization, collagen fibril assembly, and biomineralization whereas those under-represented were extracellular matrix-associated proteins. More specifically, transforming growth factor-beta 2, a member of the TGFβ family involved in both mineralization and fibrosis was strongly increased in samples from GFs of ERS patients and so were various known targets of the TGFβ signaling pathway including Collagens, Matrix metallopeptidase 2 and Fibronectin. For the over-expressed proteins quantitative RT-PCR analysis showed increased transcript levels, suggesting increased synthesis and this was further confirmed at the tissue level. Additional immunohistochemical and western blot analyses showed activation and nuclear localization of the classical TGFβ effector phospho-Smad3 in both ERS gingival tissue and ERS GFs. Exposure of the mutant cells to TGFB1 further upregulated the expression of TGFβ targets suggesting that this pathway could be a central player in the pathogenesis of the ERS gingival fibromatosis. In conclusion our data strongly suggest that TGFβ -induced modifications of the extracellular matrix contribute to the pathogenesis of ERS. To our knowledge this is the first proteomic-based analysis of FAM20A-associated modifications.
Topics: Adolescent; Amelogenesis Imperfecta; Dental Enamel Proteins; Extracellular Matrix; Fibroblasts; Fibromatosis, Gingival; Gingiva; Humans; Male; Mutation; Nephrocalcinosis; Proteomics; Signal Transduction; Transforming Growth Factor beta; Young Adult
PubMed: 34777248
DOI: 10.3389/fendo.2021.752568 -
Pediatric Dentistry 2014The purposes of this study were to: (1) investigate adhesion through shear bond strength (SBS) testing of a resin composite bonded with a self-etching bonding system... (Comparative Study)
Comparative Study
PURPOSE
The purposes of this study were to: (1) investigate adhesion through shear bond strength (SBS) testing of a resin composite bonded with a self-etching bonding system (SEB) to amelogenesis imperfecta (AI)-affected deproteinized mouse enamel or dentin; and (2) compare wild-type (WT), amelogenin null (AmelxKO), and matrix metalloproteinase-20 null (Mmp20KO) enamel and dentin phenotypes using micro-CT and nanoindentation.
METHODS
Enamel incisor surfaces of WT, AmelxKO, and Mmp20KO mice were treated with SEB with and without sodium hypochlorite and tested for SBS. Incisor dentin was also treated with SEB and tested for SBS. These surfaces were further examined by scanning electron miscroscopy. Micro-CT and nanoindentation analyses were performed on mouse dentin and enamel. Data were analyzed for significance by analysis of variance.
RESULTS
Deproteinization did not improve SBS of SEB to these AI-affected enamel surfaces. SBS of AmelxKO teeth was similar in dentin and enamel; however, it was higher in Mmp20KO dentin. The nanohardness of knockout enamel was significantly lower than WT, while knockout dentin nanohardness was not different from WT.
CONCLUSIONS
Using animal amelogenesis imperfecta models, enamel sodium hypochlorite deproteinization of hypoplastic and hypoplastic-hypomaturation enamel did not increase shear bond strength, while removal of the defective enamel allowed optimal dentin bonding.
Topics: Adhesiveness; Amelogenesis Imperfecta; Amelogenin; Animals; Composite Resins; Dental Bonding; Dental Enamel; Dental Materials; Dentin; Hardness; Incisor; Matrix Metalloproteinase 20; Mice; Mice, Knockout; Microscopy, Electron, Scanning; Oxidants; Phenotype; Resin Cements; Shear Strength; Sodium Hypochlorite; Stress, Mechanical; Surface Properties; X-Ray Microtomography
PubMed: 25303500
DOI: No ID Found -
American Journal of Medical Genetics.... Sep 2020The spectrum of peroxisomal disorders is wide and comprises individuals that die in the first year of life, as well as people with sensorineural hearing loss, retinal...
The spectrum of peroxisomal disorders is wide and comprises individuals that die in the first year of life, as well as people with sensorineural hearing loss, retinal dystrophy and amelogenesis imperfecta. In this article, we describe three patients; two diagnosed with Heimler syndrome and a third one with a mild-intermediate phenotype. We arrived at these diagnoses by conducting complete ophthalmic (National Eye Institute), auditory (National Institute of Deafness and Other Communication Disorders), and dental (National Institute of Dental and Craniofacial Research) evaluations, as well as laboratory and genetic testing. Retinal degeneration with macular cystic changes, amelogenesis imperfecta, and sensorineural hearing loss were features shared by the three patients. Patients A and C had pathogenic variants in PEX1 and Patient B, in PEX6. Besides analyzing these cases, we review the literature regarding mild peroxisomal disorders, their pathophysiology, genetics, differential diagnosis, diagnostic methods, and management. We suggest that peroxisomal disorders are considered in every child with sensorineural hearing loss and retinal degeneration. These patients should have a dental evaluation to rule out amelogenesis imperfecta as well as audiologic examination and laboratory testing including peroxisomal biomarkers and genetic testing. Appropriate diagnosis can lead to better genetic counseling and management of the associated comorbidities.
Topics: ATPases Associated with Diverse Cellular Activities; Adolescent; Adult; Amelogenesis Imperfecta; Child; Female; Genetic Counseling; Hearing Loss, Sensorineural; Humans; Male; Membrane Proteins; Nails, Malformed; Pedigree; Peroxisomal Disorders; Phenotype; Retinal Degeneration; Young Adult
PubMed: 32866347
DOI: 10.1002/ajmg.c.31823 -
Scientific Reports Jul 2017Amelogenesis imperfecta (AI), characterized by a deficiency in the quantity and/or quality of dental enamel, is genetically heterogeneous and phenotypically variable....
Amelogenesis imperfecta (AI), characterized by a deficiency in the quantity and/or quality of dental enamel, is genetically heterogeneous and phenotypically variable. The most severe type, hypocalcified AI, is mostly caused by truncating mutations in the FAM83H gene. This study aimed to identify genetic mutations in four Chinese families with hypocalcified AI. We performed mutation analysis by sequencing the candidate FAM83H gene. Three novel mutations (c.931dupC, p.V311Rfs*13; c.1130_1131delinsAA, p.S377X; and c.1147 G > T, p.E383X) and one previously reported mutation (c.973 C > T, p.R325X) in the last exon of FAM83H gene were identified. Furthermore, constructs expressing Green fluorescent protein (GFP)-tagged wild-type and three novel mutant FAM83Hs were transfected into rat dental epithelial cells (SF2 cells). Wild-type FAM83H-GFP was localized exclusively in the cytoplasm, especially in the area surrounding the nucleus, while the mutant FAM83H-GFPs (p.V311Rfs*13, p.S377X, and p.E383X) were localized predominantly in the nucleus, with lower levels in the cytoplasm.
Topics: Alleles; Amelogenesis Imperfecta; Amino Acid Substitution; Animals; Child; DNA Mutational Analysis; Female; Genes, Reporter; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Male; Mutation; Pedigree; Phenotype; Proteins; Rats; Recombinant Fusion Proteins
PubMed: 28729668
DOI: 10.1038/s41598-017-05208-0 -
Contemporary Clinical Dentistry 2018Amelogenesis imperfecta is a genetic condition affecting the teeth resulting in aberrations of the structure and clinical appearance of enamel. The treatment of...
Amelogenesis imperfecta is a genetic condition affecting the teeth resulting in aberrations of the structure and clinical appearance of enamel. The treatment of amelogenesis imperfecta involves a multidisciplinary treatment approach requiring a comprehensive examination, diagnosis, and effective treatment planning strategy along with satisfaction of patient-related factors. The clinical case described here involves judicious involvement of different disciplines to formulate a treatment plan best suitable to confirm with the patient's needs and expectations, at the same time maintaining the integrity and harmony of associated hard and soft tissues.
PubMed: 29599599
DOI: 10.4103/ccd.ccd_787_17 -
Human Genetics May 2019Amelogenesis imperfecta (AI) refers to a genetically and clinically heterogeneous group of inherited disorders affecting the structure, composition, and quantity of...
Amelogenesis imperfecta (AI) refers to a genetically and clinically heterogeneous group of inherited disorders affecting the structure, composition, and quantity of tooth enamel. Both non-syndromic and syndromic forms of AI have been described and several genes affecting various aspects of the enamel physiology have been reported. Genetically modified murine models of various genes have provided insights into the complex regulation of proper amelogenesis. Non-syndromic AI occurs spontaneously also in dogs with known recessive variants in ENAM and SLC24A4 genes. Unlike rodents with a reduced dentition and continuously erupting incisors, canine models are valuable for human AI due to similarity in the dental anatomy including deciduous and permanent teeth. We have performed a series of clinical and genetic analyses to investigate AI in several breeds of dogs and describe here two novel recessive variants in the ENAM and ACP4 genes. A fully segregating missense variant (c.716C>T) in exon 8 of ENAM substitutes a well-conserved proline to leucine, p.(Pro239Leu), resulting in a clinical hypomineralization of teeth. A 1-bp insertion in ACP4 (c.1189dupG) is predicted to lead to a frameshift, p.(Ala397Glyfs), resulting in an abnormal C-terminal part of the protein, and hypoplastic AI. The ENAM variant was specific for Parson Russell Terriers with a carrier frequency of 9%. The ACP4 variant was found in two breeds, Akita and American Akita with a carrier frequency of 22%. These genetic findings establish novel canine models of human AI with a particular interest in the case of the ACP4-deficient model, since ACP4 physiology is poorly characterized in human AI. The affected dogs could also serve as preclinical models for novel treatments while the breeds would benefit from genetic tests devised here for veterinary diagnostics and breeding programs.
Topics: Amelogenesis Imperfecta; Animals; Dental Enamel; Dental Enamel Proteins; Disease Models, Animal; Dogs; Frameshift Mutation; Genotype; Humans; Mutation, Missense; Tartrate-Resistant Acid Phosphatase
PubMed: 30877375
DOI: 10.1007/s00439-019-01997-8 -
Journal of Dental Research Jun 2019Amelogenesis imperfecta (AI) is a heterogeneous group of inherited disorders characterized by abnormal formation of dental enamel, either in isolation or as part of a...
Amelogenesis imperfecta (AI) is a heterogeneous group of inherited disorders characterized by abnormal formation of dental enamel, either in isolation or as part of a syndrome. Heterozygous variants in laminin subunit beta 3 ( LAMB3) cause AI with dominant inheritance in the absence of other cosegregating clinical features. In contrast, biallelic loss-of-function variants in LAMB3 cause recessive junctional epidermolysis bullosa, characterized by life-threatening skin fragility. We identified 2 families segregating autosomal dominant AI with variable degrees of a distinctive hypoplastic phenotype due to pathogenic variants in LAMB3. Whole exome sequencing revealed a nonsense variant (c.3340G>T, p.E1114*) within the final exon in family 1, while Sanger sequencing in family 2 revealed a variant (c.3383-1G>A) in the canonical splice acceptor site of the final exon. Analysis of cDNA from family 2 revealed retention of the final intron leading to a premature termination codon. Two unerupted third molar teeth from individual IV:5 in family 2 were subject to computerized tomography and scanning electron microscopy. LAMB3 molar teeth have a multitude of cusps versus matched controls. LAMB3 enamel was well mineralized but pitted. The architecture of the initially secreted enamel was abnormal, with cervical enamel appearing much less severely affected than coronal enamel. This study further defines the variations in phenotype-genotype correlation for AI due to variants in LAMB3, underlines the clustering of nonsense and frameshift variants causing AI in the absence of junctional epidermolysis bullosa, and highlights the shared AI phenotype arising from variants in genes coding for hemidesmosome proteins.
Topics: Amelogenesis Imperfecta; Cell Adhesion Molecules; Codon, Nonsense; Female; Frameshift Mutation; Heterozygote; Humans; Male; Pedigree; Phenotype; Kalinin
PubMed: 30905256
DOI: 10.1177/0022034519835205