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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 -
Developmental Dynamics : An Official... Oct 2021Mutation in Odontogenesis-associated phosphoprotein (ODAPH) has been reported to cause recessive hypomineralized amelogenesis imperfecta (AI) in human. However, the...
BACKGROUND
Mutation in Odontogenesis-associated phosphoprotein (ODAPH) has been reported to cause recessive hypomineralized amelogenesis imperfecta (AI) in human. However, the exact role of ODAPH in amelogenesis is still unknown.
RESULTS
ODAPH was identified as a novel constituent of the atypical basal lamina located at the interface between maturation ameloblasts and the enamel by dual immunofluorescence staining of ODAPH and LAMC2. Odaph knockout mice were generated to explore the function of ODAPH in amelogenesis. Odaph mice teeth showed severely attrition and reduced enamel mineralization. Histological analysis showed from transition or early-maturation stage, ameloblasts were rapidly shortened, lost cell polarity, and exhibited cell pathology. Abundant enamel matrix marked by amelogenin was retained. Temporary cyst-like structures were formed between flattened epithelial cells and the enamel from maturation stage to eruption. The integrity of the atypical basal lamina was impaired indicated by the reduced diffuse expression of LAMC2 and AMTN. The expression of maturation stage related genes of Amtn, Klk4, Integrinβ6 and Slc24a4 were significantly decreased.
CONCLUSIONS
Our results suggested Odaph played vital roles during amelogenesis by maintaining the integrity of the atypical basal lamina in maturation stage, which may contribute to a better understanding of the pathophysiology of human AI.
Topics: Ameloblasts; Amelogenesis; Animals; Dental Enamel; Extracellular Matrix Proteins; Laminin; Mice; Mice, Knockout; Phosphoproteins
PubMed: 33772937
DOI: 10.1002/dvdy.336 -
Children (Basel, Switzerland) Mar 2022Amelogenesis imperfecta (AI) is a heterogeneous group of rare genetic disorders affecting amelogenesis during dental development. Therefore, the molecular genetic...
Amelogenesis imperfecta (AI) is a heterogeneous group of rare genetic disorders affecting amelogenesis during dental development. Therefore, the molecular genetic etiology of AI can provide information about the nature and progress of the disease. To confirm the genetic etiology of AI in a Korean family with an autosomal dominant inheritance, pedigree and mutational analyses were performed. DNA was isolated from the participating family members and whole-exome sequencing was performed with the DNA sample of the father of the proband. The identified mutation was confirmed by Sanger sequencing. The mutational analysis revealed a novel nonsense mutation in the FAM83H gene (NM_198488.5: c.1363C > T, p.(Gln455*)), confirming autosomal dominant hypocalcified AI. Full-mouth restorative treatments of the affected children were performed after the completion of the deciduous dentition. Early diagnosis of AI can be useful for understanding the nature of the disease and for managing the condition and treatment planning.
PubMed: 35327801
DOI: 10.3390/children9030429 -
Indian Journal of Nephrology 2017Bartter's syndrome is an autosomal recessive renal tubular disorder characterized by hypokalemia, hypochloremia, metabolic alkalosis, and hyperreninemia with normal...
Bartter's syndrome is an autosomal recessive renal tubular disorder characterized by hypokalemia, hypochloremia, metabolic alkalosis, and hyperreninemia with normal blood pressure. Bartter's syndrome is associated with hypercalciuria and nephrocalcinosis. Amelogenesis imperfecta (AI) is a group of hereditary disorders that affect dental enamel. AI could be part of several syndromes. The enamel renal syndrome is the association of AI and nephrocalcinosis. We report two patients of AI with Bartter's syndrome.
PubMed: 28904439
DOI: 10.4103/ijn.IJN_203_16 -
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 -
Oral Diseases Nov 2018To delineate orodental features, dental mineral density, genetic aetiology and cellular characteristics associated with amelogenesis imperfecta (AI).
OBJECTIVE
To delineate orodental features, dental mineral density, genetic aetiology and cellular characteristics associated with amelogenesis imperfecta (AI).
MATERIALS AND METHODS
Three affected patients in a family were recruited. Whole-exome sequencing was used to identify mutations confirmed by Sanger sequencing. The proband's teeth were subjected for mineral density analysis by microcomputerised tomography and characterisation of periodontal ligament cells (PDLCs).
RESULTS
The patients presented yellow-brown, pitted and irregular enamel. A novel nonsense mutation, c.1261G>T, p.E421*, in exon 5 of the FAM83H was identified. The mineral density of the enamel was significantly decreased in the proband. The patient's PDLCs (FAM83H cells) exhibited reduced ability of cell proliferation and colony-forming unit compared with controls. The formation of stress fibres was remarkably present. Upon cultured in osteogenic induction medium, FAM83H cells, at day 7 compared to day 3, had a significant reduction of BSP, COL1 and OCN mRNA expression and no significant change in RUNX2. The upregulation of ALP mRNA levels and mineral deposition were comparable between FAM83H and control cells.
CONCLUSIONS
We identified the novel mutation in FAM83H associated with autosomal dominant hypocalcified AI. The FAM83H cells showed reduced cell proliferation and expression of osteogenic markers, suggesting altered PDLCs in FAM83H-associated AI.
Topics: Amelogenesis Imperfecta; Cell Proliferation; Cells, Cultured; Codon, Nonsense; Collagen Type I; Female; Humans; Integrin-Binding Sialoprotein; Male; Osteocalcin; Periodontal Ligament; Proteins; Stress Fibers; Exome Sequencing; Young Adult
PubMed: 29949226
DOI: 10.1111/odi.12926 -
Human Genetics May 2019
Special issue on canine genetics: animal models for human disease and gene therapies, new discoveries for canine inherited diseases, and standards and guidelines for clinical genetic testing for domestic dogs.
Topics: Amelogenesis Imperfecta; Animals; Cardiomyopathies; Crosses, Genetic; Disease Models, Animal; Dogs; Gene Deletion; Genetic Predisposition to Disease; Genetic Testing; Genetic Therapy; Genetics; Humans; Hyperekplexia; Mutation; Mutation, Missense; Retinitis Pigmentosa
PubMed: 31056728
DOI: 10.1007/s00439-019-02025-5 -
World Journal of Clinical Cases Jan 2015Superficial stains and irregularities of the enamel are generally what prompt patients to seek dental intervention to improve their smile. These stains or defects may be... (Review)
Review
Superficial stains and irregularities of the enamel are generally what prompt patients to seek dental intervention to improve their smile. These stains or defects may be due to hypoplasia, amelogenesis imperfecta, mineralized white spots, or fluorosis, for which enamel microabrasion is primarily indicated. Enamel microabrasion involves the use of acidic and abrasive agents, such as with 37% phosphoric acid and pumice or 6% hydrochloric acid and silica, applied to the altered enamel surface with mechanical pressure from a rubber cup coupled to a rotatory mandrel of a low-rotation micromotor. If necessary, this treatment can be safely combined with bleaching for better esthetic results. Recent studies show that microabrasion is a conservative treatment when the enamel wear is minimal and clinically imperceptible. The most important factor contributing to the success of enamel microabrasion is the depth of the defect, as deeper, opaque stains, such as those resulting from hypoplasia, cannot be resolved with microabrasion, and require a restorative approach. Surface enamel alterations that result from microabrasion, such as roughness and microhardness, are easily restored by saliva. Clinical studies support the efficacy and longevity of this safe and minimally invasive treatment. The present article presents the clinical and scientific aspects concerning the microabrasion technique, and discusses the indications for and effects of the treatment, including recent works describing microscopic and clinical evaluations.
PubMed: 25610848
DOI: 10.12998/wjcc.v3.i1.34 -
International Journal of Molecular... Feb 2021Amelogenesis imperfecta is a congenital form of enamel hypoplasia. Although a number of genetic mutations have been reported in humans, the regulatory network of these...
Amelogenesis imperfecta is a congenital form of enamel hypoplasia. Although a number of genetic mutations have been reported in humans, the regulatory network of these genes remains mostly unclear. To identify signatures of biological pathways in amelogenesis imperfecta, we conducted bioinformatic analyses on genes associated with the condition in humans. Through an extensive search of the main biomedical databases, we found 56 genes in which mutations and/or association/linkage were reported in individuals with amelogenesis imperfecta. These candidate genes were further grouped by function, pathway, protein-protein interaction, and tissue-specific expression patterns using various bioinformatic tools. The bioinformatic analyses highlighted a group of genes essential for extracellular matrix formation. Furthermore, advanced bioinformatic analyses for microRNAs (miRNAs), which are short non-coding RNAs that suppress target genes at the post-transcriptional level, predicted 37 candidates that may be involved in amelogenesis imperfecta. To validate the miRNA-gene regulation association, we analyzed the target gene expression of the top seven candidate miRNAs: miR-3195, miR-382-5p, miR-1306-5p, miR-4683, miR-6716-3p, miR-3914, and miR-3935. Among them, miR-1306-5p, miR-3195, and miR-3914 were confirmed to regulate ameloblast differentiation through the regulation of genes associated with amelogenesis imperfecta in AM-1 cells, a human ameloblastoma cell line. Taken together, our study suggests a potential role for miRNAs in amelogenesis imperfecta.
Topics: Ameloblasts; Amelogenesis Imperfecta; Cell Differentiation; Cell Line; Computational Biology; Humans; MicroRNAs; Protein Interaction Maps; Reproducibility of Results
PubMed: 33672174
DOI: 10.3390/ijms22042202 -
PloS One 2017Amelogenesis imperfecta is a group of disorders causing abnormalities in enamel formation in various phenotypes. Many mutations in the FAM83H gene have been identified...
Amelogenesis imperfecta is a group of disorders causing abnormalities in enamel formation in various phenotypes. Many mutations in the FAM83H gene have been identified to result in autosomal dominant hypocalcified amelogenesis imperfecta in different populations. However, the structure and function of FAM83H and its pathological mechanism have yet to be further explored. Evolutionary analysis is an alternative for revealing residues or motifs that are important for protein function. In the present study, we chose 50 vertebrate species in public databases representative of approximately 230 million years of evolution, including 1 amphibian, 2 fishes, 7 sauropsidas and 40 mammals, and we performed evolutionary analysis on the FAM83H protein. By sequence alignment, conserved residues and motifs were indicated, and the loss of important residues and motifs of five special species (Malayan pangolin, platypus, minke whale, nine-banded armadillo and aardvark) was discovered. A phylogenetic time tree showed the FAM83H divergent process. Positive selection sites in the C-terminus suggested that the C-terminus of FAM83H played certain adaptive roles during evolution. The results confirmed some important motifs reported in previous findings and identified some new highly conserved residues and motifs that need further investigation. The results suggest that the C-terminus of FAM83H contain key conserved regions critical to enamel formation and calcification.
Topics: Amelogenesis Imperfecta; Amino Acid Motifs; Amphibians; Animals; Biological Evolution; Conserved Sequence; Dental Enamel; Fishes; Gene Expression; Humans; Mammals; Mutation; Phylogeny; Proteins; Reptiles; Sequence Alignment; Sequence Homology, Amino Acid
PubMed: 28683132
DOI: 10.1371/journal.pone.0180360