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Clinical Oral Investigations Jun 2022This study aimed to comprehensively characterise genetic variants of amelogenesis imperfecta in a single Korean family through whole-exome sequencing and bioinformatics...
OBJECTIVES
This study aimed to comprehensively characterise genetic variants of amelogenesis imperfecta in a single Korean family through whole-exome sequencing and bioinformatics analysis.
MATERIAL AND METHODS
Thirty-one individuals of a Korean family, 9 of whom were affected and 22 unaffected by amelogenesis imperfecta, were enrolled. Whole-exome sequencing was performed on 12 saliva samples, including samples from 8 affected and 4 unaffected individuals. The possible candidate genes associated with the disease were screened by segregation analysis and variant filtering. In silico mutation impact analysis was then performed on the filtered variants based on sequence conservation and protein structure.
RESULTS
Whole-exome sequencing data revealed an X-linked dominant, heterozygous genomic missense mutation in the mitochondrial gene holocytochrome c synthase (HCCS). We also found that HCCS is potentially related to the role of mitochondria in amelogenesis. The HCCS variant was expected to be deleterious in both evolution-based and large population-based analyses. Further, the variant was predicted to have a negative effect on catalytic function of HCCS by in silico analysis of protein structure. In addition, HCCS had significant association with amelogenesis in literature mining analysis.
CONCLUSIONS
These findings suggest new evidence for the relationship between amelogenesis and mitochondria function, which could be implicated in the pathogenesis of amelogenesis imperfecta.
CLINICAL RELEVANCE
The discovery of HCCS mutations and a deeper understanding of the pathogenesis of amelogenesis imperfecta could lead to finding solutions for the fundamental treatment of this disease. Furthermore, it enables dental practitioners to establish predictable prosthetic treatment plans at an early stage by early detection of amelogenesis imperfecta through personalised medicine.
Topics: Amelogenesis Imperfecta; Dentists; Humans; Lyases; Mutation; Professional Role; Republic of Korea
PubMed: 35243551
DOI: 10.1007/s00784-022-04413-0 -
Journal of Dental Research Aug 2019Enamel formation and quality are dependent on environmental conditions, including exposure to fluoride, which is a widespread natural element. Fluoride is routinely used...
Enamel formation and quality are dependent on environmental conditions, including exposure to fluoride, which is a widespread natural element. Fluoride is routinely used to prevent caries. However, when absorbed in excess, fluoride may also lead to altered enamel structural properties associated with enamel gene expression modulations. As iron plays a determinant role in enamel quality, the aim of our study was to evaluate the iron metabolism in dental epithelial cells and forming enamel of mice exposed to fluoride, as well as its putative relation with enamel mechanical properties. Iron storage was investigated in dental epithelial cells with Perl's blue staining and secondary ion mass spectrometry imaging. Iron was mainly stored by maturation-stage ameloblasts involved in terminal enamel mineralization. Iron storage was drastically reduced by fluoride. Among the proteins involved in iron metabolism, ferritin heavy chain (Fth), in charge of iron storage, appeared as the preferential target of fluoride according to quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry analyses. Fluorotic enamel presented a decreased quantity of iron oxides attested by electron spin resonance technique, altered mechanical properties measured by nanoindentation, and ultrastructural defects analyzed by scanning electron microscopy and energy dispersive x-ray spectroscopy. The in vivo functional role of Fth was illustrated with mice, which incorporated less iron into their dental epithelium and exhibited poor enamel quality. These data demonstrate that exposure to excessive fluoride decreases ameloblast iron storage, which contributes to the defective structural and mechanical properties in rodent fluorotic enamel. They raise the question of fluoride's effects on iron storage in other cells and organs that may contribute to its effects on population health.
Topics: Ameloblasts; Amelogenesis; Animals; Epithelial Cells; Fluorides; Fluorosis, Dental; Iron; Male; Mice; Mice, Inbred BALB C
PubMed: 31329045
DOI: 10.1177/0022034519855650 -
The Chinese Journal of Dental Research Mar 2024To investigate FAM20A gene variants and histological features of amelogenesis imperfecta and to further explore the functional impact of these variants.
OBJECTIVE
To investigate FAM20A gene variants and histological features of amelogenesis imperfecta and to further explore the functional impact of these variants.
METHODS
Whole-exome sequencing (WES) and Sanger sequencing were used to identify pathogenic gene variants in three Chinese families with amelogenesis imperfecta. Bioinformatics analysis, in vitro histological examinations and experiments were conducted to study the functional impact of gene variants, and the histological features of enamel, keratinised oral mucosa and dental follicle.
RESULTS
The authors identified two nonsense variants c. 406C > T (p.Arg136*) and c.826C > T (p.Arg176*) in a compound heterozygous state in family 1, two novel frameshift variants c.936dupC (p.Val313Argfs*67) and c.1483dupC (p.Leu495Profs*44) in a compound heterozygous state in family 2, and a novel homozygous frameshift variant c.530_531insGGTC (p.Ser178Valfs*21) in family 3. The enamel structure was abnormal, and psammomatoid calcifications were identified in both the gingival mucosa and dental follicle. The bioinformatics and subcellular localisation analyses indicated these variants to be pathogenic. The secondary and tertiary structure analysis speculated that these five variants would cause structural damage to FAM20A protein.
CONCLUSION
The present results broaden the variant spectrum and clinical and histological findings of diseases associated with FAM20A, and provide useful information for future genetic counselling and functional investigation.
Topics: Humans; Amelogenesis Imperfecta; Calcification, Physiologic; Computational Biology; Dental Enamel; Dental Enamel Proteins; East Asian People
PubMed: 38546520
DOI: 10.3290/j.cjdr.b5136761 -
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 -
BDJ Open Apr 2023To characterize phenotype and genotype of amelogenesis imperfecta (AI) in a Thai patient, and review of literature.
OBJECTIVES
To characterize phenotype and genotype of amelogenesis imperfecta (AI) in a Thai patient, and review of literature.
MATERIALS AND METHODS
Variants were identified using trio-exome and Sanger sequencing. The ITGB6 protein level in patient's gingival cells was measured. The patient's deciduous first molar was investigated for surface roughness, mineral density, microhardness, mineral composition, and ultrastructure.
RESULTS
The patient exhibited hypoplastic-hypomineralized AI, taurodontism, and periodontal inflammation. Exome sequencing identified the novel compound heterozygous ITGB6 mutation, a nonsense c.625 G > T, p.(Gly209*) inherited from mother and a splicing c.1661-3 C > G from father, indicating AI type IH. The ITGB6 level in patient cells was significantly reduced, compared with controls. Analyses of a patient's tooth showed a significant increase in roughness while mineral density of enamel and microhardness of enamel and dentin were significantly reduced. In dentin, carbon was significantly decreased while calcium, phosphorus, and oxygen levels were significantly increased. Severely collapsed enamel rods and a gap in dentinoenamel junction were observed. Of six affected families and eight ITGB6 variants that have been reported, our patient was the only one with taurodontism.
CONCLUSION
We report the hypoplasia/hypomineralization/taurodontism AI patient with disturbed tooth characteristics associated with the novel ITGB6 variants and reduced ITGB6 expression, expanding genotype, phenotype, and understanding of autosomal recessive AI.
PubMed: 37041139
DOI: 10.1038/s41405-023-00142-y -
Journal of Pharmacy & Bioallied Sciences Nov 2021Calcium and phosphate are the major components of hydroxyapatite crystals that form the inorganic portion of the teeth. Apart from these, certain elements are present in... (Review)
Review
Calcium and phosphate are the major components of hydroxyapatite crystals that form the inorganic portion of the teeth. Apart from these, certain elements are present in little amounts in enamel and dentin of the human teeth. Although they are required in minute quantities, their absence may alter healthy development of enamel and dentin and may result in developmental tooth defects as well as dental caries. Furthermore, excessive intake of some trace elements may inversely affect tooth development and health. The exact of effects that trace elements have on teeth and oral health is still an unexplored territory. The present paper reviews the presence of trace elements in teeth and their role in tooth health and development.
PubMed: 35017905
DOI: 10.4103/jpbs.jpbs_392_21 -
Journal of Materials Science. Materials... Aug 2021Caries and dental erosion are common oral diseases. Traditional treatments involve the mechanical removal of decay and filling but these methods are not suitable for... (Review)
Review
Caries and dental erosion are common oral diseases. Traditional treatments involve the mechanical removal of decay and filling but these methods are not suitable for cases involving large-scale enamel erosion, such as hypoplasia. To develop a noninvasive treatment, promoting remineralisation in the early stage of caries is of considerable clinical significance. Therefore, biomimetic mineralisation is an ideal approach for restoring enamel. Biomimetic mineralisation forms a new mineral layer that is tightly attached to the surface of the enamel. This review details the state-of-art achievements on the application of amelogenin and non-amelogenin, amorphous calcium phosphate, ions flow and other techniques in the biomimetic mineralisation of enamel. The ultimate goal of this review was to shed light on the requirements for enamel biomineralisation. Hence, herein, we summarise two strategies of biological minimisation systems for in situ enamel restoration inspired by amelogenesis that have been developed in recent years and compare their advantages and disadvantages.
Topics: Amelogenesis; Amelogenin; Animals; Biomimetic Materials; Biomimetics; Calcification, Physiologic; Calcium Phosphates; Dental Enamel; Dental Restoration, Permanent; Humans
PubMed: 34455518
DOI: 10.1007/s10856-021-06583-x -
Journal of Medical Case Reports Oct 2023Metabolic bone disease causes significant morbidity and mortality, especially when misdiagnosed. With genetic testing, multiple disease pathologies can be analyzed.
BACKGROUND
Metabolic bone disease causes significant morbidity and mortality, especially when misdiagnosed. With genetic testing, multiple disease pathologies can be analyzed.
CASE PRESENTATION
A 5-year and 9-month-old otherwise healthy Yemeni girl presented to her Yemen physician for evaluation of inward bending of her right knee and short stature. After extensive medical testing, she was given a diagnosis of hypophosphatemic rickets and growth hormone deficiency and started on treatment. Despite appropriate treatment, however, her condition continued to progress, prompting her family to pursue additional workup including genetic testing outside of Yemen. Genetic testing ultimately revealed a variation of unknown significance associated with amelogenesis imperfecta.
CONCLUSIONS
Hypophosphatemic rickets secondary to renal tubular acidosis was the working diagnosis. However, the patient's condition did not improve. Further genetic testing revealed a variation of unknown significance associated with amelogenesis imperfecta. We aim to present this case, provide an overview of the causes, and diagnostic metabolic bone health evaluation.
Topics: Female; Humans; Infant; Amelogenesis Imperfecta; Rickets, Hypophosphatemic; Acidosis, Renal Tubular; Diagnostic Errors
PubMed: 37858137
DOI: 10.1186/s13256-023-04164-w -
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 -
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