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BACKGROUND: This manuscript investigates the prevalence, classification, accompanying findings, and treatment modalities associated with infraoccluded primary molars. The aim of this study categorizing primary molars based on the severity of infraocclusion and assessing their respective treatment interventions across different severity groups. METHODS: The classification, treatment types, accompanying findings, and the condition of succeeding premolars of infraoccluded molars were documented. Chi-square tests, including Fisher's Exact Chi-square test, Fisher Freeman Halton Exact Chi-square test, and One Sample Chi-square test, were conducted. The predetermined significance level was less than 0.05. RESULTS: The study population consisted of 3132 subjects aged 3 to 15 years, with a prevalence of 4.3% for infraocclusion. Infraocclusion typically manifests between 6 and 9 years of age and predominantly affects mandibular primary molars. Treatment interventions varied based on infraocclusion severity, with more invasive procedures required for severe cases. Accompanying findings associated with infraocclusion include adjacent teeth tipping, significant deviation in midline shifts towards the affected side and increased caries. Additionally, succeeding premolar agenesis was observed in 2% of infraoccluded molars, with extraction rates higher in cases where the successor tooth was mesially or distally located. CONCLUSIONS: The study offers novel insights to dental practitioners concerning the severity and distribution of treatment interventions for infraocclusion. It suggests that more severe cases may necessitate more invasive procedures, with the aim of enhancing patient outcomes through timely intervention and personalized therapeutic strategies.
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Má Oclusão , Dente Molar , Dente Decíduo , Humanos , Criança , Dente Molar/patologia , Adolescente , Feminino , Masculino , Prevalência , Pré-Escolar , Dente Decíduo/patologia , Má Oclusão/terapia , Má Oclusão/epidemiologia , Má Oclusão/classificação , Índice de Gravidade de DoençaRESUMO
OBJECTIVES: This retrospective study aimed to (i) survey the correlation between decayed, missing, filled teeth (DMFT), and presence of first permanent molars (FPMs) with poor prognosis and (ii) evaluate the treatment requirements. MATERIALS AND METHODS: Seven hundred seventy-three children with fully erupted FPMs were included in this study. DMFT for the permanent dentition, FPMs, and Global DMFT were evaluated based on clinical and radiographic evaluation. The ratio of deep dentin caries (DDC) and apical lesion presence among FPMs, including treatment requirements, were analysed. Spearman rank correlation coefficient and t tests were used for statistical analysis. RESULTS: The caries prevalence was found at 61.4%, where the mean DMFT was calculated as 1.89 ± 2.15. There was a positive correlation between DMFT values and age (rs = 0.27). On the other hand, there was a negative correlation between global DMFT values and age (rs = - 0.29). Regarding treatment needs of FPM with poor prognosis, 12.03% of the teeth needed pulpectomy, 8.93% pulpotomy, 8.93% pulp capping, and 5.3% extraction. Having higher DMFT values was correlated significantly (p < 0.01) with the presence of DDC (rs = 0.50) and apical lesion (rs = 0.34). Susceptibility to DDC and apical lesions was significantly higher at mandible than maxilla (p < 0.01). The correlation was significant between DMFT values and apical lesion presence (p < 0.01). CONCLUSION: The ratio of FPMs with poor prognosis was found high in the study group. Treatment requirements of FPMs increased with age, and pulp interventions often took part in the majority. This study successfully concluded that higher DMFT values were correlated with the presence of DDC and apical lesion. CLINICAL RELEVANCE: FPMs with poor prognosis demonstrate a risk factor for apical lesion presence.
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Cárie Dentária , Dente Molar , Criança , Índice CPO , Assistência Odontológica , Cárie Dentária/epidemiologia , Cárie Dentária/terapia , Dentição Permanente , Humanos , Dente Molar/diagnóstico por imagem , Prevalência , Prognóstico , Estudos RetrospectivosRESUMO
OBJECTIVES: This retrospective study aimed to evaluate the effect of COVID-19 pandemic on dental attendance and emergency/non-emergency visits of children during the outbreak, compared to the same period of 2019. MATERIALS AND METHODS: Patients who visited the paediatric department clinic during the observed period were included in this study. The patient's demographic data, purpose of visit, and treatment type were evaluated retrospectively from patient examination records. The Pearson chi-square and t-tests were used for comprehensive statistical analysis. RESULTS: A total of 1454 patient files (1184/270 cases from non-pandemic/pandemic period) were assessed. A significant reduction was found in aggregated emergency/non-emergency visits during the pandemic period (p < 0.01). During the pandemic, average daily visits for emergency dental care were observed to have a decrease to half of the non-pandemic period. Non-emergency routine dental visits have also exhibited a drastic decline. Severe dental pain due to pulpal inflammation and abscess/swelling were the most frequently reported urgent dental complaints that patients applied to the paediatric dental clinic during the pandemic period. CONCLUSION: COVID-19 pandemic has a significant influence on patients' attendance to paediatric dental clinic. Therefore, concerning a potential post-pandemic increase in treatment demand, meticulous future planning and proper regulation of dental care should be provided for better oral health and children's quality of life. CLINICAL RELEVANCE: This study's importance is the observation of dramatically reduced number of patient visits during the pandemic period which may yield increased number of oral health-related complications in the long run.
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COVID-19 , Pandemias , Criança , Humanos , Qualidade de Vida , Estudos Retrospectivos , SARS-CoV-2RESUMO
OBJECTIVES: This retrospective study aimed to evaluate health status as a new patient risk factor and analyze its influence on the survival of posterior composite restorations in patients with early childhood caries (ECC). MATERIALS AND METHODS: Patients who received dental treatment of ECC under general anesthesia (GA) and attended at least one follow-up visit were included in this study. A total of 907 patient records were evaluated retrospectively through patient examination forms and panoramic radiographs. Kaplan-Meier survival probability analysis with log-rank test was used to assess the posterior composite restorations' longevity up to 24 months. Furthermore, risk factors were determined using Cox regression multivariate analysis. RESULTS: A total of 5063 posterior composite restorations were assessed. Following the Cox regression analysis to determine the effect of risk factors on longevity of composite restorations, findings revealed that the survival probability of composite fillings was significantly lower in patients with systemic disease (p = 0.00). Filling materials were compared based on the survival probabilities and results were further discussed. There was no significant relationship between age, gender, and the survival of the restoration; however, the child's health status (p = 0.00) and caries risk status (p = 0.05) significantly affected survival. Moreover, the type of arch and pulp intervention influenced the restoration's survival. CONCLUSION: Systemic disease has a detrimental influence over longevity of composite restorations. Therefore, considering the reduced survival rates of the composite restorations for children who have systemic disease, alternative non-invasive treatment options should be considered. CLINICAL RELEVANCE: This study's novelty is the observation of drastically reduced survival of composite restorations in children with systemic disease.
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Suscetibilidade à Cárie Dentária , Cárie Dentária , Criança , Pré-Escolar , Resinas Compostas , Cárie Dentária/terapia , Falha de Restauração Dentária , Restauração Dentária Permanente , Humanos , Estudos RetrospectivosRESUMO
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.
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Amelogênese Imperfeita/diagnóstico , Amelogênese Imperfeita/genética , Genes Recessivos , Estudos de Associação Genética , Predisposição Genética para Doença , Mutação , Receptores do Fator de Necrose Tumoral/genética , Consanguinidade , Genótipo , Mutação em Linhagem Germinativa , Humanos , Hibridização In Situ , Linhagem , Fenótipo , Splicing de RNA , Sequenciamento do ExomaRESUMO
Clinically, primary and permanent teeth are distinct anatomically and the presentation of caries lesions differs between the two dentitions. Hence, the possibility exists that genetic contributions to tooth formation of the two dentitions are different. The purpose of this study was to test the hypothesis that genetic associations with an artificial caries model will not be the same between primary and permanent dentitions. Enamel samples from primary and permanent teeth were tested for microhardness at baseline, after carious lesion creation, and after fluoride application to verify association with genetic variants of selected genes. Associations were found between genetic variants of ameloblastin, amelogenin, enamelin, tuftelin, tuftelin interactive protein 11, and matrix metallopeptidase 20 and enamel from permanent teeth but not with enamel from primary teeth. In conclusion, our data continue to support that genetic variation may impact enamel development and consequently individual caries susceptibility. These effects may be distinct between primary and permanent dentitions.
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BACKGROUND: Congenital forms of hearing impairment can be caused by mutations in the estrogen related receptor beta (ESRRB) gene. Our initial linkage studies suggested the ESRRB locus is linked to high caries experience in humans. METHODS: We tested for association between the ESRRB locus and dental caries in 1,731 subjects, if ESRRB was expressed in whole saliva, if ESRRB was associated with the microhardness of the dental enamel, and if ESRRB was expressed during enamel development of mice. RESULTS: Two families with recessive ESRRB mutations and DFNB35 hearing impairment showed more extensive dental destruction by caries. Expression levels of ESRRB in whole saliva samples showed differences depending on sex and dental caries experience. CONCLUSIONS: The common etiology of dental caries and hearing impairment provides a venue to assist in the identification of individuals at risk to either condition and provides options for the development of new caries prevention strategies, if the associated ESRRB genetic variants are correlated with efficacy.
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Cárie Dentária/genética , Perda Auditiva Neurossensorial/patologia , Receptores de Estrogênio/genética , Desmineralização do Dente/genética , Adolescente , Adulto , Animais , Linhagem Celular Tumoral , Criança , Pré-Escolar , Cromossomos Humanos Par 14 , Esmalte Dentário/crescimento & desenvolvimento , Feminino , Estudos de Associação Genética , Perda Auditiva Neurossensorial/genética , Humanos , Desequilíbrio de Ligação , Masculino , Camundongos , Linhagem , Polimorfismo de Nucleotídeo Único , Receptores de Estrogênio/fisiologia , Adulto JovemRESUMO
Amelogenesis imperfecta (AI) is a genetically and clinically heterogeneous group of inherited dental enamel defects without any other nonoral symptoms. Recently, a disease-causing nonsense mutation (c.406C>T) in a novel gene, FAM20A, was identified in a large consanguineous family affected by AI with gingival hyperplasia. We performed mutational analyses on nine AI families with similar phenotypes and identified three homozygous mutations (c.34_35delCT, c.813-2A>G, c.1175_1179delGGCTC) in three families and a compound heterozygous mutation (c.[590-2A>G] + [c.826C>T]) in one family. An in vitro splicing assay with a minigene confirmed the mutations located in the splicing acceptor site caused the deletion of exons 3 and 6, respectively. Taking into consideration the locations of the nonsense and frameshift mutations, the mutant transcripts are most likely degraded by nonsense-mediated mRNA degradation and it results in a loss of the FAM20A protein. This study confirms the importance of the FAM20A protein in enamel biomineralization as well as tooth eruption.
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Amelogênese Imperfeita/genética , Proteínas do Esmalte Dentário/genética , Mutação da Fase de Leitura , Deleção de Sequência , Sequência de Bases , Códon sem Sentido , Consanguinidade , Análise Mutacional de DNA , Éxons , Heterozigoto , Homozigoto , Humanos , Dados de Sequência Molecular , Linhagem , Fenótipo , República da CoreiaRESUMO
Molar incisor hypomineralization (MIH) is an enamel condition characterized by lesions ranging in color from white to brown which present rapid caries progression, and mainly affects permanent first molars and incisors. These enamel defects usually occur when there are disturbances during the mineralization or maturation stage of amelogenesis. Both genetic and environmental factors have been suggested to play roles in MIH's development, but no conclusive risk factors have shown the source of the disease. During head and neck development, the interferon regulatory factor 6 (IRF6) gene is involved in the structure formation of the oral and maxillofacial regions, and the transforming growth factor alpha (TGFA) is an essential cell regulator, acting during proliferation, differentiation, migration and apoptosis. In this present study, it was hypothesized that these genes interact and contribute to predisposition of MIH. Environmental factors affecting children that were 3 years of age or older were also hypothesized to play a role in the disease etiology. Those factors included respiratory issues, malnutrition, food intolerance, infection of any sort and medication intake. A total of 1,065 salivary samples from four different cohorts were obtained, and DNA was extracted from each sample and genotyped for nine different single nucleotide polymorphisms. Association tests and logistic regression implemented in PLINK were used for analyses. A potential interaction between TGFA rs930655 with all markers tested in the cohort from Turkey was identified. These interactions were not identified in the remaining cohorts. Associations (p<0.05) between the use of medication after three years of age and MIH were also found, suggesting that conditions acquired at the age children start to socialize might contribute to the development of MIH.
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Hipoplasia do Esmalte Dentário/genética , Interação Gene-Ambiente , Genótipo , Incisivo/crescimento & desenvolvimento , Dente Molar/crescimento & desenvolvimento , Polimorfismo de Nucleotídeo Único , Fator de Crescimento Transformador alfa/genética , Adolescente , Amelogênese/genética , Criança , Feminino , Humanos , Incisivo/patologia , Masculino , Dente Molar/patologiaRESUMO
OBJECTIVES: The purpose of this study was to determine if shear bond resistance of orthodontic brackets bonded to enamel is associated with genes implicated in the enamel mineralization process. METHODS: Ninety-two permanent, caries-free premolars extracted for orthodontic purposes and their associated saliva samples were obtained. Eighteen single nucleotide polymorphisms (SNPs) were studied for association with shear bond resistance. The genes of interest in this study were those previously associated with dental caries by our group. All tooth samples were bonded on the buccal surface with metallic lower lateral brackets, and then subjected to physical debonding. The force required to debond the bracket was recorded in Newtons (N) and converted to a shear bond resistance value in Megapascals (N/mm2). The data were analyzed for statistical significance as compared with the mean shear bond resistance value via PLINK whole genome analysis software. RESULTS: Associations were found between the SNPs for tuftelin (rs7526319, P = 0.004) and amelogenin (rs17878486, P = 0.04) and a higher shear bond resistance. CONCLUSION: The collected data support the proposed hypothesis that genes involved in the mineralization process affect the bonding of orthodontic brackets, and such an association is of value for the field of orthodontics, particularly in evaluating the efficacy of enamel-resin bond strength for patients receiving treatment.
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Esmalte Dentário/fisiologia , Braquetes Ortodônticos/efeitos adversos , Polimorfismo de Nucleotídeo Único , Calcificação de Dente/genética , Adolescente , Estudos Transversais , Feminino , Humanos , Masculino , Fatores de Risco , Resistência ao Cisalhamento , Desmineralização do Dente/genéticaRESUMO
PURPOSE: The low salivary pH and buffering capacity are caused by using heart failure medications. For this reason oral health should be supported in cardiac patients, it is necessary that they attend dental clinics for regular follow up. The aim of this study is to evaluate the relationship between the salivary oxidative stress markers and salivary pH, salivary buffering capacity, salivary flow rate and dental caries of children with congenital heart disease (CHD). MATERIALS AND METHODS: This cross sectional study was carried out with 42 CHD and 42 healthy children. The participants' gender, age, general health and medications, and caries scores (dfs/ DMFS) were written down, then their unstimulated saliva samples were collected. These specimens were evaluated in terms of the salivary secretion rate, salivary buffering capacity, pH, protein levels, superoxide dismutase (SOD), ferric reducing antioxidant power (FRAP), the thiobarbituric acid reactive substances (TBARS), protein carbonyl, protein thiols, total sialic acid. RESULTS: Both groups showed caries at similar levels. The salivary pH and buffering capacity were significantly less in the children with CHD than in the controls. The levels of TBARS and protein carbonyl were significantly higher in the children with CHD than in the controls. There was not any significant difference relating to the mean salivary secretion rate, protein levels, SOD, FRAP, protein thiols and total sialic acid. CONCLUSION: The elevated TBARS and protein carbonyl levels in the patients with CHD were observed as an indicator of the free radical damage leading to oxidative stress.
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OBJECTIVE: The goal of the present work was to use dental conditions that have been independently associated with cleft lip and palate (CL/P) as a tool to identify a broader collection of individuals to be used for gene identification that lead to clefts. STUDY DESIGN: We studied 1573 DNA samples combining individuals that were born with CL/P or had tooth agenesis, supernumerary teeth, molar incisor hypomineralization, or dental caries with the goal to identify genetic associations. We tested 2 single-nucleotide polymorphisms that were located in the vicinity of regions suggested to contribute to supernumerary teeth. Overrepresentation of alleles were determined for combinations of individuals as well as for each individual phenotypic group with an α of .05. RESULTS: We determined that the allele C of rs622260 was overrepresented in all individuals studied compared with a group of unrelated individuals who did not present any of the conditions described earlier. When subgroups were tested, associations were found for individuals with hypomineralization. CONCLUSIONS: Although we did not test this hypothesis directly in the present study, based on associations reported previously, we believe that CL/P is actually a syndrome of alterations of the dentition, and considering it that way may allow for the identification of genotype-phenotype correlations that may be useful for clinical care.
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Fenda Labial/genética , Fissura Palatina/genética , Cárie Dentária/genética , Imunoglobulinas/genética , Proteínas do Tecido Nervoso/genética , Polimorfismo de Nucleotídeo Único , Anormalidades Dentárias/genética , Alelos , Feminino , Genótipo , Humanos , Masculino , Fenótipo , SíndromeRESUMO
We have previously shown that AQP5 and BTF3 genetic variation and expression in whole saliva are associated with caries experience suggesting that these genes may have a functional role in protecting against caries. To further explore these results, we tested ex vivo if variants in these genes are associated with subclinical dental enamel mineral loss. DNA and enamel samples were obtained from 53 individuals. Enamel samples were analyzed for Knoop hardness of sound enamel, integrated mineral loss after subclinical carious lesion creation, and change in integrated mineral loss after remineralization. DNA samples were genotyped for single nucleotide polymorphisms using TaqMan chemistry. Chi-square and Fisher's exact tests were used to compare individuals above and below the mean sound enamel microhardness of the cohort with alpha of 0.05. The A allele of BTF3 rs6862039 appears to be associated with harder enamel at baseline (p = 0.09), enamel more resistant to demineralization (p = 0.01), and enamel that more efficiently regain mineral and remineralize (p = 0.04). Similarly, the G allele of AQP5 marker rs3759129 and A allele of AQP5 marker rs296763 are associated with enamel more resistant to demineralization (p = 0.03 and 0.05, respectively). AQP5 and BTF3 genetic variations influence the initial subclinical stages of caries lesion formation in the subsurface of enamel.
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Aquaporins (AQP) are water channel proteins and the genes coding for AQP2, AQP5, and AQP6 are clustered in 12q13. Since AQP5 is expressed in serous acinar cells of salivary glands, we investigated its involvement in caries. DNA samples from 1,383 individuals from six groups were studied. Genotypes of eight single nucleotide polymorphisms covering the aquaporin locus were tested for association with caries experience. Interaction with genes involved in enamel formation was tested. The association between enamel microhardness at baseline, after creation of artificial caries lesion, and after exposure to fluoride and the genetic markers in AQP5 was tested. Finally, AQP5 expression in human whole saliva, after exposure to fluoride in a mammary gland cell line, which is known to express AQP5, and in Wistar rats was also verified. Nominal associations were found between caries experience and markers in the AQP5 locus. Since these associations suggested that AQP5 may be inhibited by levels of fluoride in the drinking water that cause fluorosis, we showed that fluoride levels above optimal levels change AQP5 expression in humans, cell lines, and rats. We have shown that AQP5 is involved in the pathogenesis of caries and likely interacts with fluoride.
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Aquaporina 5/metabolismo , Cárie Dentária/metabolismo , Fluoretos/metabolismo , Adolescente , Adulto , Animais , Aquaporina 5/genética , Linhagem Celular Tumoral , Criança , Pré-Escolar , Cárie Dentária/genética , Feminino , Marcadores Genéticos/genética , Genótipo , Humanos , Masculino , Glândulas Mamárias Humanas/metabolismo , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Ratos , Ratos Wistar , Saliva/metabolismo , Adulto JovemRESUMO
The aim of this clinical case series is to present a diagnosis and different treatment methods of patients in different ages with amelogenesis imperfecta (AI) as well as further treatments during a 3-6 years follow-up period. A number of 31 patients (16 female, 15 male with a mean age of 10.77 ± 2.65 years) with AI have been examined for the study group between 2007 and 2010 years. A detailed anamnesis was recorded, followed by a clinical and radiological assessment of oral health. The types of AI classified for each patient according to clinical and radiographic evaluation. The main complaints of patients, presence of dental caries and dental anomalies were noted. Necessary treatments had been planned for the individual cases of AI. A number of 19 patients had hypoplastic (HP) form, and 10 patients showed hypomaturation (HM) form of AI, while one patient showed hypocalcified form of AI and one patient had HM-HP form with taurodontism. Main complaints were chiefly related to dissatisfactory esthetics and dental sensitivity. Caries prevalence index was 93.5%. Mean decayed, missing, filling permanent teeth (DMF) and DMF surface (DMFS) were found as 2.74 ± 1.71 and 6.23 ± 3.99; df (decayed, filling primary teeth) and dfs (decayed, filling primary teeth surface) were found as 3.12 ± 2.85 and 5.24 ± 4.97, respectively. All patients received individual clinical care, including preventive, restorative, and prosthetic treatments. Patients have scheduled for regular follow-up in every 3 months. Composite restorations were used as the most common treatment (25 patients, 80.6%). The treatment plan should be based on patient's age, type of defects and individual needs of the patients. Necessary treatment plan is essential, not only due to functional and aesthetic reasons, but also for the positive psychological impact on young patients.
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Genetic disturbances during dental development influence variation of number and shape of the dentition. In this study, we tested if genetic variation in enamel formation genes is associated with molar-incisor hypomineralization (MIH), also taking into consideration caries experience. DNA samples from 163 cases with MIH and 82 unaffected controls from Turkey, and 71 cases with MIH and 89 unaffected controls from Brazil were studied. Eleven markers in five genes [ameloblastin (AMBN), amelogenin (AMELX), enamelin (ENAM), tuftelin (TUFT1), and tuftelin-interacting protein 11 (TFIP11)] were genotyped by the TaqMan method. Chi-square was used to compare allele and genotype frequencies between cases with MIH and controls. In the Brazilian data, distinct caries experience within the MIH group was also tested for association with genetic variation in enamel formation genes. The ENAM rs3796704 marker was associated with MIH in both populations (Brazil: p=0.03; OR=0.28; 95% C.I.=0.06-1.0; Turkey: p=1.22e-012; OR=17.36; 95% C.I.=5.98-56.78). Associations between TFIP11 (p=0.02), ENAM (p=0.00001), and AMELX (p=0.01) could be seen with caries independent of having MIH or genomic DNA copies of Streptococcus mutans detected by real time PCR in the Brazilian sample. Several genes involved in enamel formation appear to contribute to MIH.
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Amelogênese/genética , Hipoplasia do Esmalte Dentário/genética , Expressão Gênica , Adulto , Amelogenina , Brasil , Estudos de Casos e Controles , Proteínas do Esmalte Dentário/genética , Proteínas da Matriz Extracelular , Feminino , Frequência do Gene , Variação Genética , Genótipo , Humanos , Masculino , Proteínas Nucleares , Proteínas/genética , Fatores de Processamento de RNA , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Risco , Streptococcus mutans/genética , Turquia , Adulto JovemRESUMO
Amelogenesis imperfecta (AI) is a group of inherited conditions featuring isolated enamel malformations. About 5% of AI cases show an X-linked pattern of inheritance, which are caused by mutations in AMELX. In humans there are two, non-allelic amelogenin genes: AMELX (Xp22.3) and AMELY (Yp11.2). About 90% of amelogenin expression is from AMELX, which is nested within intron 1 of the gene encoding Rho GTPase activating protein 6 (ARHGAP6). We recruited two AI families and determined that their disease-causing mutations were partial deletions in ARHGAP6 that completely deleted AMELX. Affected males in both families had a distinctive enamel phenotype resembling "snow-capped" teeth. The 96,240 bp deletion in family 1 was confined to intron 1 of ARHGAP6 (g.302534_398773del96240), but removed alternative ARHGAP6 promoters 1c and 1d. Analyses of developing teeth in mice showed that ARHGAP6 is not expressed from these promoters in ameloblasts. The 52,654 bp deletion in family 2 (g.363924_416577del52654insA) removed ARHGAP6 promoter 1d and exon 2, precluding normal expression of ARHGAP6. The male proband of family 2 had slightly thinner enamel with greater surface roughness, but exhibited the same pattern of enamel malformations characteristic of males in family 1, which themselves showed minor variations in their enamel phenotypes. We conclude that the enamel defects in both families were caused by amelogenin insufficiency, that deletion of AMELX results in males with a characteristic snow-capped enamel phenotype, and failed ARHGAP6 expression did not appreciably alter the severity of enamel defects when AMELX was absent.