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Journal of Personalized Medicine Dec 2021Amelogenesis imperfecta (AI) is a rare genetic condition affecting the quantity and/or quality of tooth enamel. Hypomaturation AI is characterized by brownish-yellow...
Amelogenesis imperfecta (AI) is a rare genetic condition affecting the quantity and/or quality of tooth enamel. Hypomaturation AI is characterized by brownish-yellow discoloration with increased opacity and poorly mineralized enamel prone to fracture and attrition. We recruited three families affected by hypomaturation AI and performed whole exome sequencing with selected individuals in each family. Bioinformatic analysis and Sanger sequencing identified and confirmed mutations and segregation in the families. Family 1 had a novel homozygous frameshift mutation in gene (NM_003485.3:c.78_83delinsC, p.(Val27Cysfs*146)). Family 2 had a novel homozygous nonsense mutation in gene (NM_153646.4:c.613C>T, NP_705932.2:p.(Arg205*)). Family 3 also had a homozygous missense mutation in gene which was reported previously (c.437C>T, p.(Ala146Val)). This report not only expands the mutational spectrum of the AI-causing genes but also improves our understanding of normal and pathologic amelogenesis.
PubMed: 35055328
DOI: 10.3390/jpm12010013 -
The Cochrane Database of Systematic... Jun 2013Amelogenesis imperfecta (AI) is a tooth development disorder in which the teeth are covered with thin, abnormally formed enamel. This enamel is easily fractured and... (Review)
Review
BACKGROUND
Amelogenesis imperfecta (AI) is a tooth development disorder in which the teeth are covered with thin, abnormally formed enamel. This enamel is easily fractured and damaged, which affects the appearance of the teeth, especially if left untreated. Negative psychological outcomes, due to compromised appearance and function, in patients with AI, have been found to compromise a person's attractiveness and reduce social interaction. The treatment used depends on the severity of the problem.
OBJECTIVES
To compare the success rates of different restorative materials and techniques used for the restoration of anterior and posterior teeth with AI in terms of patient satisfaction (aesthetics and sensitivity) and function.
SEARCH METHODS
We searched the Cochrane Oral Health Group's Trials Register (to 18 April 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 3), MEDLINE via OVID (1946 to 18 April 2013), EMBASE via OVID (1980 to 18 April 2013), CINAHL via EBSCO (1980 to 18 April 2013), Abstracts of the Conference Proceedings of the International Association for Dental Research (2001 to 18 April 2013) and reference lists of relevant articles. There were no restrictions on language or date of publication in the electronic searches.
SELECTION CRITERIA
Randomised controlled trials where children and adolescents with AI who required restoration of teeth were allocated to different restoration techniques would have been selected. Outcomes which would have been evaluated were patient satisfaction, aesthetics, masticatory function and longevity of restorations.
DATA COLLECTION AND ANALYSIS
Two review authors would have extracted data and assessed the risk of bias in included studies independently. Disagreement between the two authors would have been resolved by consulting a third review author. First authors were contacted for additional information and unpublished data.
MAIN RESULTS
No studies met the inclusion criteria for this review.
AUTHORS' CONCLUSIONS
We found no randomised controlled trials of restorative treatments for children and adolescents with AI, and therefore there is no evidence as to which is the best restoration. Well defined randomised controlled trials which recruit children and adolescents and focus on the type and severity of the disorder should be undertaken to determine the best intervention for restoring teeth affected by AI.
Topics: Adolescent; Amelogenesis Imperfecta; Child; Humans; Treatment Outcome
PubMed: 23744349
DOI: 10.1002/14651858.CD007157.pub2 -
Journal of Dental Research May 2019Dental enamel malformations, or amelogenesis imperfecta (AI), can be isolated or syndromic. To improve the prospects of making a successful diagnosis by genetic testing,...
Dental enamel malformations, or amelogenesis imperfecta (AI), can be isolated or syndromic. To improve the prospects of making a successful diagnosis by genetic testing, it is important that the full range of genes and mutations that cause AI be determined. Defects in WDR72 (WD repeat-containing protein 72; OMIM *613214) cause AI, type IIA3 (OMIM #613211), which follows an autosomal recessive pattern of inheritance. The defective enamel is normal in thickness, severely hypomineralized, orange-brown stained, and susceptible to attrition. We identified 6 families with biallelic WDR72 mutations by whole exome sequence analyses that perfectly segregated with the enamel phenotype. The novel mutations included 3 stop-gains [NM_182758.2: c.377G>A/p.(Trp126*), c.1801C>T/p.(Arg601*), c.2350A>T/p.(Arg784*)], a missense mutation [c.1265G>T/p.(Gly422Val)], and a 62,138-base pair deletion (NG_017034.2: g.35441_97578del62138) that removed WDR72 coding exons 3 through 13. A previously reported WDR72 frameshift was also observed [c.1467_1468delAT/p.(Val491Aspfs*8)]. Three of the affected patients showed decreased serum pH, consistent with a diagnosis of renal tubular acidosis. Percentiles of stature and body weight varied among 8 affected individuals but did not show a consistent trend. These studies support that WDR72 mutations cause a syndromic form of AI and improve our ability to diagnose AI caused by WDR72 defects.
Topics: Acidosis; Amelogenesis Imperfecta; Humans; Mutation; Pedigree; Proteins
PubMed: 30779877
DOI: 10.1177/0022034518824571 -
International Journal of Clinical... 2022Amelogenesis imperfecta (AI) is an inherited dental condition affecting enamel, which can result in significant tooth discoloration and enamel breakdown, requiring...
UNLABELLED
Amelogenesis imperfecta (AI) is an inherited dental condition affecting enamel, which can result in significant tooth discoloration and enamel breakdown, requiring lifelong dental care. Distal renal tubular acidosis (dRTA) is a condition in which the kidneys are unable to acidify the urine to a pH < 5.5 in the presence of systemic metabolic acidosis. Management of AI and dRTA patients requires both medical and dental expertise to achieve long-term successful results. The aim of this paper is to present the dental management of a child with AI and dRTA.
HOW TO CITE THIS ARTICLE
Nadaf N, Krishnapriya V, Chandra A, Amelogenesis Imperfecta and Distal Renal Tubular Acidosis. Int J Clin Pediatr Dent 2022;15(1):121-123.
PubMed: 35528488
DOI: 10.5005/jp-journals-10005-2171 -
Journal of Dental Research Jan 2022Amelogenesis imperfecta (AI) is an innate disorder that affects the formation and mineralization of the tooth enamel. When diagnosed with AI, one's teeth can be...
Amelogenesis imperfecta (AI) is an innate disorder that affects the formation and mineralization of the tooth enamel. When diagnosed with AI, one's teeth can be hypoplastic (thin enamel), hypomature (normal enamel thickness but discolored and softer than normal enamel), hypocalcified (normal enamel thickness but extremely weak), or mixed conditions of the above. Numerous studies have revealed the genes that are involved in causing AI. Recently, (acid phosphatase 4) was newly found as a gene causing hypoplastic AI, and it was suggested that mutant forms of ACP4 might affect access to the catalytic core or the ability to form a homodimer. In this study, a Korean and a Turkish family with hypoplastic AI were recruited, and their exome sequences were analyzed. Biallelic mutations were revealed in : paternal (NM_033068: c.419C>T, p.(Pro140Leu)) and maternal (c.262C>A, p.(Arg88Ser)) mutations in family 1 and a paternal (c.713C>T, p.(Ser238Leu)) mutation and de novo (c.350A>G, p.(Gln117Arg)) mutation in the maternal allele in family 2. Mutations were analyzed by cloning, mutagenesis, immunofluorescence, immunoprecipitation, and acid phosphatase activity test. Comparison between the wild-type and mutant ACP4s showed a decreased amount of protein expression from the mutant forms, a decreased ability to form a homodimer, and a decreased acid phosphatase activity level. We believe that these findings will not only expand the mutational spectrum of but also increase our understanding of the mechanism of ACP4 function during normal and pathologic amelogenesis.
Topics: Acid Phosphatase; Amelogenesis Imperfecta; Dental Enamel; Humans; Mutation; Pedigree; Tooth
PubMed: 34036831
DOI: 10.1177/00220345211015119 -
Proceedings of the National Academy of... Dec 2022The outstanding mechanical and chemical properties of dental enamel emerge from its complex hierarchical architecture. An accurate, detailed multiscale model of the...
The outstanding mechanical and chemical properties of dental enamel emerge from its complex hierarchical architecture. An accurate, detailed multiscale model of the structure and composition of enamel is important for understanding lesion formation in tooth decay (dental caries), enamel development (amelogenesis) and associated pathologies (e.g., amelogenesis imperfecta or molar hypomineralization), and minimally invasive dentistry. Although features at length scales smaller than 100 nm (individual crystallites) and greater than 50 µm (multiple rods) are well understood, competing field of view and sampling considerations have hindered exploration of mesoscale features, i.e., at the level of single enamel rods and the interrod enamel (1 to 10 µm). Here, we combine synchrotron X-ray diffraction at submicrometer resolution, analysis of crystallite orientation distribution, and unsupervised machine learning to show that crystallographic parameters differ between rod head and rod tail/interrod enamel. This variation strongly suggests that crystallites in different microarchitectural domains also differ in their composition. Thus, we use a dilute linear model to predict the concentrations of minority ions in hydroxylapatite (Mg and CO/Na) that plausibly explain the observed lattice parameter variations. While differences within samples are highly significant and of similar magnitude, absolute values and the sign of the effect for some crystallographic parameters show interindividual variation that warrants further investigation. By revealing additional complexity at the rod/interrod level of human enamel and leaving open the possibility of modulation across larger length scales, these results inform future investigations into mechanisms governing amelogenesis and introduce another feature to consider when modeling the mechanical and chemical performance of enamel.
Topics: Humans; Dental Caries; Crystallography; Amelogenesis Imperfecta; Amelogenesis; Dental Enamel
PubMed: 36534796
DOI: 10.1073/pnas.2211285119 -
Frontiers in Physiology 2023Amelogenesis imperfecta (AI) is a heterogeneous group of genetic rare diseases disrupting enamel development (Smith et al., Front Physiol, 2017a, 8, 333). The clinical...
Amelogenesis imperfecta (AI) is a heterogeneous group of genetic rare diseases disrupting enamel development (Smith et al., Front Physiol, 2017a, 8, 333). The clinical enamel phenotypes can be described as hypoplastic, hypomineralized or hypomature and serve as a basis, together with the mode of inheritance, to Witkop's classification (Witkop, J Oral Pathol, 1988, 17, 547-553). AI can be described in isolation or associated with others symptoms in syndromes. Its occurrence was estimated to range from 1/700 to 1/14,000. More than 70 genes have currently been identified as causative. We analyzed using next-generation sequencing (NGS) a heterogeneous cohort of AI patients in order to determine the molecular etiology of AI and to improve diagnosis and disease management. Individuals presenting with so called "isolated" or syndromic AI were enrolled and examined at the Reference Centre for Rare Oral and Dental Diseases (O-Rares) using D4/phenodent protocol (www.phenodent.org). Families gave written informed consents for both phenotyping and molecular analysis and diagnosis using a dedicated NGS panel named GenoDENT. This panel explores currently simultaneously 567 genes. The study is registered under NCT01746121 and NCT02397824 (https://clinicaltrials.gov/). GenoDENT obtained a 60% diagnostic rate. We reported genetics results for 221 persons divided between 115 AI index cases and their 106 associated relatives from a total of 111 families. From this index cohort, 73% were diagnosed with non-syndromic amelogenesis imperfecta and 27% with syndromic amelogenesis imperfecta. Each individual was classified according to the AI phenotype. Type I hypoplastic AI represented 61 individuals (53%), Type II hypomature AI affected 31 individuals (27%), Type III hypomineralized AI was diagnosed in 18 individuals (16%) and Type IV hypoplastic-hypomature AI with taurodontism concerned 5 individuals (4%). We validated the genetic diagnosis, with class 4 (likely pathogenic) or class 5 (pathogenic) variants, for 81% of the cohort, and identified candidate variants (variant of uncertain significance or VUS) for 19% of index cases. Among the 151 sequenced variants, 47 are newly reported and classified as class 4 or 5. The most frequently discovered genotypes were associated with and for isolated AI. and genes were the most frequent genes identified for syndromic AI. Patients negative to the panel were resolved with exome sequencing elucidating for example the gene involved ie or digenic inheritance. NGS GenoDENT panel is a validated and cost-efficient technique offering new perspectives to understand underlying molecular mechanisms of AI. Discovering variants in genes involved in syndromic AI ( ) transformed patient overall care. Unravelling the genetic basis of AI sheds light on Witkop's AI classification.
PubMed: 37228816
DOI: 10.3389/fphys.2023.1130175 -
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 -
Journal of Dentistry Jun 2024To summarize studies published between 2017 and 2023 examining the clinical diagnosis and restorative management of amelogenesis imperfecta (AI) in children and... (Review)
Review
OBJECTIVE
To summarize studies published between 2017 and 2023 examining the clinical diagnosis and restorative management of amelogenesis imperfecta (AI) in children and adolescents.
DATA
The review incorporated publications on clinical diagnosis, patient-reported outcomes, clinical trials, cohort studies, and case reports that included individuals below 19 years of age with non-syndromic AI.
SOURCES
A literature search was conducted across electronic databases, PubMed, Web of Science, and CINAHL, including papers published between 2017-2023. The search yielded 335 unique results, of which 38 were eligible for inclusion.
RESULTS
New evidence on the genetic background of AI makes it now advisable to recommend genetic testing to supplement a clinical AI diagnosis. The discussions of the dental profession and the public on social media do not always incorporate recent scientific evidence. Interview studies are finding that the impact of AI on quality of life is more severe than previously appreciated. New evidence suggests that single-tooth ceramic crowns should be the first choice of treatment. Due to incomplete reporting, case reports have been of limited value.
CONCLUSION
In young patients with AI symptoms of pain and hypersensitivity decreased, and aesthetics were improved following all types of restorative therapy. Resin composite restorations were mainly performed in cases with hypoplastic AI and mild symptoms. Single tooth ceramic crown restorations have a high success rate in all types of AI and can be used in young individuals with AI.
CLINICAL SIGNIFICANCE
Prosthetic rehabilitation in adolescents with severe AI is cost effective, improves esthetics, reduces tooth sensitivity, and improves oral health-related quality of life.
PubMed: 38909645
DOI: 10.1016/j.jdent.2024.105149 -
Human Mutation May 2021Amelogenesis imperfecta (AI) describes a heterogeneous group of developmental enamel defects that typically have Mendelian inheritance. Exome sequencing of 10 families...
Amelogenesis imperfecta (AI) describes a heterogeneous group of developmental enamel defects that typically have Mendelian inheritance. Exome sequencing of 10 families with recessive hypomaturation AI revealed four novel and one known variants in the matrix metallopeptidase 20 (MMP20) gene that were predicted to be pathogenic. MMP20 encodes a protease that cleaves the developing extracellular enamel matrix and is necessary for normal enamel crystal growth during amelogenesis. New homozygous missense changes were shared between four families of Pakistani heritage (c.625G>C; p.(Glu209Gln)) and two of Omani origin (c.710C>A; p.(Ser237Tyr)). In two families of UK origin and one from Costa Rica, affected individuals were homozygous for the previously reported c.954-2A>T; p.(Ile319Phefs*19) variant. For each of these variants, microsatellite haplotypes appeared to exclude a recent founder effect, but elements of haplotype were conserved, suggesting more distant founding ancestors. New compound heterozygous changes were identified in one family of the European heritage: c.809_811+12delinsCCAG; p.(?) and c.1122A>C; p.(Gln374His). This report further elucidates the mutation spectrum of MMP20 and the probable impact on protein function, confirms a consistent hypomaturation phenotype and shows that mutations in MMP20 are a common cause of autosomal recessive AI in some communities.
Topics: Amelogenesis Imperfecta; Founder Effect; Homozygote; Humans; Matrix Metalloproteinase 20; Pedigree
PubMed: 33600052
DOI: 10.1002/humu.24187