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British Dental Journal Aug 2018Genetic testing is increasingly applied across healthcare reflecting the value to diagnosis, clinical decision-making, service organisation and advancement of the...
INTRODUCTION
Genetic testing is increasingly applied across healthcare reflecting the value to diagnosis, clinical decision-making, service organisation and advancement of the research-informed evidence base. Patient expectations are changing. Genetic testing has not been part of dental practice. Introduction of an NHS-targeted gene panel test for amelogenesis imperfecta (AI), a heterogeneous genetic disorder affecting enamel appearance and function, represents a paradigm shift. This impacts on specialists in paediatric dentistry and other members of the dental team delivering longitudinal care for individuals with AI.
AIM
To evaluate the opinions of paediatric dentists on genetic testing for dental conditions using AI as the exemplar.
METHOD
Two focus groups of nine UK NHS paediatric dentists each were audio recorded (September 2016) and transcribed verbatim. Qualitative analysis was undertaken using Interpretative Phenomenological Analysis (IPA).
RESULTS
A wide range of views reflected existing insight and understanding. Three core concepts of justification, ownership and challenges emerged. The clinicians were generally open to involvement with genetic testing in paediatric dentistry, but required more support.
CONCLUSION
Areas for clarification and professional development were identified as important in ensuring that genetic testing in dentistry, which is currently in its infancy, reaches translational potential and enhances patient care as this area of healthcare continues to advance rapidly.
Topics: Amelogenesis Imperfecta; Child; Dentists; Focus Groups; Genetic Testing; Health Knowledge, Attitudes, Practice; Humans; United Kingdom
PubMed: 30141472
DOI: 10.1038/sj.bdj.2018.641 -
Journal of Dental Research Oct 2014Amelogenesis imperfecta (AI) is a genetic disease affecting tooth enamel formation. AI can be an isolated entity or a phenotype of syndromes. To date, more than 10 genes...
Amelogenesis imperfecta (AI) is a genetic disease affecting tooth enamel formation. AI can be an isolated entity or a phenotype of syndromes. To date, more than 10 genes have been associated with various forms of AI. We have identified 2 unrelated Turkish families with hypoplastic AI and performed mutational analysis. Whole-exome sequencing identified 2 novel heterozygous nonsense mutations in the ENAM gene (c.454G>T p.Glu152* in family 1, c.358C>T p.Gln120* in family 2) in the probands. Affected individuals were heterozygous for the mutation in each family. Segregation analysis within each family revealed individuals with incomplete penetrance or extremely mild enamel phenotype, in spite of having the same mutation with the other affected individuals. We believe that these findings will broaden our understanding of the clinical phenotype of AI caused by ENAM mutations.
Topics: Adolescent; Amelogenesis Imperfecta; Child; Chromosome Segregation; Codon, Nonsense; Codon, Terminator; Consanguinity; Cytosine; Dental Enamel; Dental Enamel Hypoplasia; Exome; Exons; Extracellular Matrix Proteins; Female; Glutamic Acid; Glutamine; Guanine; Heterozygote; Humans; Male; Penetrance; Phenotype; Thymine
PubMed: 25143514
DOI: 10.1177/0022034514548222 -
European Archives of Paediatric... Aug 2022Dental bleaching in paediatric patients can be used to address discolouration of teeth due to trauma, endodontic treatment, or enamel and dentine defects. Despite being...
PURPOSE
Dental bleaching in paediatric patients can be used to address discolouration of teeth due to trauma, endodontic treatment, or enamel and dentine defects. Despite being a minimally invasive and successful treatment, the use of bleaching products in children and young people remains controversial. This evaluation was designed to provide insight into the child's perspective on dental bleaching and the influence that this treatment has upon their life.
METHOD
A dental bleaching patient reported outcome measure (PROM) was developed and piloted in 2019. Data were collected from 3 UK units (January-March 2020). Children attending these units for bleaching reviews were invited to complete the PROM.
RESULTS
Twenty seven PROM questionnaires were completed including 19 courses of external bleaching and 8 courses of internal/external bleaching. The average age was 14 years old (9-17 years). The common indications for bleaching were Amelogenesis Imperfecta, dental trauma and Molar Incisor Hypomineralisation. Patients reported improvements in their appearance (89%) and self-confidence (81%). Sensitivity was the most common side effect, reported in 63% of cases.
CONCLUSION
This PROM supports the use of dental bleaching in children and young people when treating dental disease that causes discolouration. Bleaching not only improved the appearance of teeth, but also patients' self-confidence. Sensitivity is a common side effect and clinicians should discuss this common risk and its management with patients and their families.
Topics: Adolescent; Amelogenesis Imperfecta; Child; Dental Enamel; Dental Enamel Hypoplasia; Humans; Patient Reported Outcome Measures; United Kingdom
PubMed: 35713847
DOI: 10.1007/s40368-022-00721-x -
International Journal of Molecular... Jun 2024mutations cause X-linked amelogenesis imperfecta (AI), known as AI types IE, IIB, and IIC in Witkop's classification, characterized by hypoplastic (reduced thickness)...
mutations cause X-linked amelogenesis imperfecta (AI), known as AI types IE, IIB, and IIC in Witkop's classification, characterized by hypoplastic (reduced thickness) and/or hypomaturation (reduced hardness) enamel defects. In this study, we conducted whole exome analyses to unravel the disease-causing mutations for six AI families. Splicing assays, immunoblotting, and quantitative RT-PCR were conducted to investigate the molecular and cellular effects of the mutations. Four pathogenic variants (NM_182680.1:c.2T>C; c.29T>C; c.77del; c.145-1G>A) and a whole gene deletion (NG_012494.2:g.307534_403773del) were identified. The affected individuals exhibited enamel malformations, ranging from thin, poorly mineralized enamel with a "snow-capped" appearance to severe hypoplastic defects with minimal enamel. The c.145-1G>A mutation caused a -1 frameshift (NP_001133.1:p.Val35Cysfs*5). Overexpression of c.2T>C and c.29T>C demonstrated that mutant amelogenin proteins failed to be secreted, causing elevated endoplasmic reticulum stress and potential cell apoptosis. This study reveals a genotype-phenotype relationship for -associated AI: While amorphic mutations, including large deletions and 5' truncations, of cause hypoplastic-hypomaturation enamel with snow-capped teeth (AI types IIB and IIC) due to a complete loss of gene function, neomorphic variants, including signal peptide defects and 3' truncations, lead to severe hypoplastic/aplastic enamel (AI type IE) probably caused by "toxic" cellular effects of the mutant proteins.
Topics: Amelogenesis Imperfecta; Humans; Amelogenin; Male; Female; Genetic Association Studies; Mutation; Pedigree; Phenotype; Child; Endoplasmic Reticulum Stress; Genotype; Exome Sequencing
PubMed: 38892321
DOI: 10.3390/ijms25116132 -
Journal of Applied Oral Science :... Apr 2019Amelogenesis imperfecta (AI) is a group of enamel development disorders that alter the structure and chemical composition of the tissue. There is great variability in...
UNLABELLED
Amelogenesis imperfecta (AI) is a group of enamel development disorders that alter the structure and chemical composition of the tissue. There is great variability in the clinical presentation; according to Witkop, AI can be categorized into 14 subtypes, which makes its diagnosis extremely complex.
OBJECTIVE
This study aimed to describe and determine the frequency of clinical and radiographic features and inheritance patterns found in 41 Chilean families diagnosed with diverse types of AI.
MATERIAL AND METHODS
We analyzed the clinical records, photographs, pedigrees and radiographs of 121 individuals recruited between 2003 and 2016. All of the information was included in a database that was analyzed using the application Stata 14.
RESULTS
The 72 affected individuals had average age of 16 years, and no sex association with the presence of AI was found. The most frequent clinical subtypes were as follows: 43% hypomature, 25% hypoplastic, 21% hypomature/hypoplastic, 7% hypocalcified and 4% hypocalcified/hypoplastic. The number of severely affected teeth was 22, which occurred in the patients with hypocalcified and hypocalcified/hypoplasic AI who presented the highest number of damaged teeth. Caries and periodontal disease were found in 47 and 32% of the patients, respectively. Malocclusions were observed in 43% of the individuals with AI, with open bite being the most frequent. Radiographically, the thickness of the enamel decreased in 51% of the patients, and 80% showed decreased radiopacity of the enamel compared to that of dentin. Autosomal dominant inheritance pattern was found in 37% of the families with hypoplastic AI, and autosomal recessive pattern was present in 56% of the other clinical subtypes, but more frequently in those affected with hypomature and hypocalcified AI.
CONCLUSION
Of the five clinical subtypes, autosomal recessive hypomature, autosomal dominant hypoplastic and autosomal recessive hypomature/hypoplastic AI were the most prevalent subtypes in this group.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amelogenesis Imperfecta; Child; Child, Preschool; Chile; Dental Enamel; Female; Genealogy and Heraldry; Humans; Inheritance Patterns; Male; Middle Aged; Phenotype; Sex Distribution; Statistics, Nonparametric; Young Adult
PubMed: 30970114
DOI: 10.1590/1678-7757-2018-0359 -
Clinical Genetics Mar 2019Amelogenesis imperfecta (AI) is a collection of isolated (non-syndromic) inherited diseases affecting dental enamel formation or a clinical phenotype in syndromic...
Amelogenesis imperfecta (AI) is a collection of isolated (non-syndromic) inherited diseases affecting dental enamel formation or a clinical phenotype in syndromic conditions. We characterized three consanguineous AI families with generalized irregular hypoplastic enamel with rapid attrition that perfectly segregated with homozygous defects in a novel gene: RELT that is a member of the tumor necrosis factor receptor superfamily (TNFRSF). RNAscope in situ hybridization of wild-type mouse molars and incisors showed specific Relt mRNA expression by secretory stage ameloblasts and by odontoblasts. Relt mice generated by CRISPR/Cas9 exhibited incisor and molar enamel malformations. Relt enamel had a rough surface and underwent rapid attrition. Normally unmineralized spaces in the deep enamel near the dentino-enamel junction (DEJ) were as highly mineralized as the adjacent enamel, which likely altered the mechanical properties of the DEJ. Phylogenetic analyses showed the existence of selective pressure on RELT gene outside of tooth development, indicating that the human condition may be syndromic, which possibly explains the history of small stature and severe childhood infections in two of the probands. Knowing a TNFRSF member is critical during the secretory stage of enamel formation advances our understanding of amelogenesis and improves our ability to diagnose human conditions featuring enamel malformations.
Topics: Amelogenesis Imperfecta; Consanguinity; Genes, Recessive; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Germ-Line Mutation; Humans; In Situ Hybridization; Mutation; Pedigree; Phenotype; RNA Splicing; Receptors, Tumor Necrosis Factor; Exome Sequencing
PubMed: 30506946
DOI: 10.1111/cge.13487 -
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