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1.
Am J Med Genet A ; 179(10): 1913-1981, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31468724

RESUMO

Dental anomalies occur frequently in a number of genetic disorders and act as major signs in diagnosing these disorders. We present definitions of the most common dental signs and propose a classification usable as a diagnostic tool by dentists, clinical geneticists, and other health care providers. The definitions are part of the series Elements of Morphology and have been established after careful discussions within an international group of experienced dentists and geneticists. The classification system was elaborated in the French collaborative network "TÊTECOU" and the affiliated O-Rares reference/competence centers. The classification includes isolated and syndromic disorders with oral and dental anomalies, to which causative genes and main extraoral signs and symptoms are added. A systematic literature analysis yielded 408 entities of which a causal gene has been identified in 79%. We classified dental disorders in eight groups: dental agenesis, supernumerary teeth, dental size and/or shape, enamel, dentin, dental eruption, periodontal and gingival, and tumor-like anomalies. We aim the classification to act as a shared reference for clinical and epidemiological studies. We welcome critical evaluations of the definitions and classification and will regularly update the classification for newly recognized conditions.

2.
Sleep Med ; 58: 123-129, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31146124

RESUMO

BACKGROUND: Sleep-disordered breathing (SDB), including obstructive sleep apnea syndrome, is often underestimated because it requires a burdensome test (ie, polysomnography) to ensure diagnosis. To improve polysomnography referral, it is of utmost importance to validate efficient alternative screening tools. This study aimed to provide a translation and a cross-cultural validation of the Pediatric Sleep Questionnaire (PSQ) into French to obtain an easy-to-use and reliable screening tool. The psychometric properties of the French version were also determined. METHODS: The process of cross-cultural adaptation was carried out following these steps: forward-backward translation, evaluation by an expert committee, and pretesting of the pre-final version. Reliability of the French-PSQ version was assessed by Cronbach's alpha coefficients and Spearman's correlation on a convenient sample of 201 children (aged between 2 and 17 years). Construct validity was determined by factor analysis of principal components. RESULTS: Internal consistency was within an adequate range for all subscales: 0.711 for snoring, 0.559 for sleepiness, 0.682 for behavioral problems, and 0.776 for the whole questionnaire. Spearman's correlation analysis comparing questionnaires administered two weeks apart showed good correlation coefficients for all subscales (snoring: 0.642, sleepiness: 0.846, behavioral problems: 0.780, and entire SRBD scale: 0.835). Factor analysis performed to assess the structure of the French-SRBD scale confirmed the same four factors described in the original questionnaire ("breathing," "behavior," "sleepiness," and "other"). CONCLUSION: The French version of the PSQ has been successfully cross-culturally adapted and showed good psychometric properties, suggesting that it is useful as a tool to screen sleep-disordered breathing in French-speaking children.

3.
BMC Oral Health ; 18(1): 211, 2018 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-30537964

RESUMO

BACKGROUND: The Parental-Caregivers Perceptions Questionnaire (P-CPQ) is a measure of parental/caregivers' perceptions of the impact of children's oral health on quality of life. The aim of the study was evaluate the psychometric properties of the French version of the P-CPQ. METHOD: The original P-CPQ was developed in English language and has 31 items divided into four sub-scales. This cross-sectional study used the translation-back translation method. The translated questionnaire was pretested on 14 parents-caregivers to obtain the final French version. The psychometric properties were tested on 142 parents/caregivers of three clinical groups of children from 8 to 10 years old without dental/facial anomalies (presumed healthy), with oral-facial clefts and with oral-dental anomalies linked to a rare disease other than cleft, approached in the waiting room of the Centre of the Hospital Rothschild in Paris, France, where the children attended treatment. Internal consistency was assessed by Cronbach's alpha and test-retest reliability by Intra-class Correlation Coefficient (ICC). Construct validity was measured by correlations between the total scores and the global ratings of oral health and overall wellbeing, and tested using exploratory factor analysis (EFA) and the factorial structure was evaluated by the partial confirmatory factor analysis (PCFA). Discriminant validity was determined using Kruskall-Wallis test. RESULTS: The mean (standard deviation) P-CPQ score was 18.73(18.79). Internal consistency was confirmed by a Cronbach alpha of 0.85. The test-retest reliability revealed that the responses to items were satisfactorily stable (ICC = 0.88). Construct validity was demonstrated by significant correlation coefficients between the total scale and the global ratings (r = 0.54 and 0.46; p < 0.001). Factor analysis with Principal Component Analysis extracted seven factors explaining 65.23% cumulative variance. Goodness-of-fit indices for partial confirmatory factor analysis were satisfactory for the 7-factors model of the French-PCPQ version. There were statistically significant differences between clinical groups regarding the total scale, thus demonstrating discriminant validity (p < 0.001). CONCLUSION: This French P-CPQ version showed reliability and validity comparable to the previous versions. However, the cross-cultural structure of the subscales should be further evaluated.


Assuntos
Saúde Bucal/estatística & dados numéricos , Pais , Qualidade de Vida/psicologia , Criança , Feminino , França/epidemiologia , Humanos , Masculino , Anormalidades da Boca/epidemiologia , Anormalidades da Boca/psicologia , Pais/psicologia , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários , Tradução
4.
Nat Commun ; 9(1): 3087, 2018 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-30082715

RESUMO

Skeletal dysplasia with multiple dislocations are severe disorders characterized by dislocations of large joints and short stature. The majority of them have been linked to pathogenic variants in genes encoding glycosyltransferases, sulfotransferases or epimerases required for glycosaminoglycan synthesis. Using exome sequencing, we identify homozygous mutations in SLC10A7 in six individuals with skeletal dysplasia with multiple dislocations and amelogenesis imperfecta. SLC10A7 encodes a 10-transmembrane-domain transporter located at the plasma membrane. Functional studies in vitro demonstrate that SLC10A7 mutations reduce SLC10A7 protein expression. We generate a Slc10a7-/- mouse model, which displays shortened long bones, growth plate disorganization and tooth enamel anomalies, recapitulating the human phenotype. Furthermore, we identify decreased heparan sulfate levels in Slc10a7-/- mouse cartilage and patient fibroblasts. Finally, we find an abnormal N-glycoprotein electrophoretic profile in patient blood samples. Together, our findings support the involvement of SLC10A7 in glycosaminoglycan synthesis and specifically in skeletal development.

5.
BMC Oral Health ; 18(1): 108, 2018 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-29907114

RESUMO

BACKGROUND: Hereditary enamel defect diseases are regrouped under the name "Amelogenesis Imperfecta" (AIH). Both dentitions are affected. Clinical expression is heterogeneous and varies between patients. Mutations responsible for this multigene disease may alter various genes and the inheritance can be either autosomal dominant or recessive, or X-linked. Until now, no therapeutic consensus has emerged for this rare disease. CASE PRESENTATION: The purpose of this article was to report treatments of AIH patients from childhood to early adulthood. Treatment of three patients of 3, 8 16 years old are described. Each therapeutic option was discussed according to patients' age and type of enamel alteration. Paediatric crowns and resin based bonding must be preferred in primary teeth. In permanent teeth, non-invasive or minimally invasive dentistry should be the first choice in order to follow a therapeutic gradient from the less invasive options to prosthodontic treatments. CONCLUSION: Functional and aesthetic issues require patients to be treated; this clinical care should be provided as early as possible to enable a harmonious growth of the maxillofacial complex and to prevent pain.

6.
Health Qual Life Outcomes ; 16(1): 86, 2018 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-29720198

RESUMO

BACKGROUND: The Child Perceptions Questionnaire (CPQ) belongs to a set of questionnaires measuring Child Oral Health Quality of Life (COHQOL). The CPQ is used to collect the perceptions of children on the impact of oral diseases on their quality of life. This cross-sectional study was aimed to translate the CPQ8-10 into French language and evaluate its psychometric properties. METHODS: The translation process complied with international recommendations. The final French version was tested on children aged 8-10 years old attending consultations in a Parisian public hospital and divided into three groups: children with oral-facial clefts, children with dental anomalies linked to a rare disease other than clefts and children presumed to be healthy and without anomalies. The internal consistency relating to the reliability of CPQ8-10 was evaluated by Cronbach's alpha. The intra-class correlation was used to measure reproducibility at the test-retest level. Construct validity was evaluated by Spearman's correlation and tested using factor analysis. The discriminant validity was assessed using Kruskall Wallis test. Criterion validity was calculated using Spearman's correlation. RESULTS: One hundred seventy-six children participated in this study. During the translation process, minor changes were made. The French version showed good reliability with a Cronbach's alpha of 0.81 for the total scale. The ICC of the test-retest was excellent (=0.90) demonstrating good reproducibility. The construct validity was acceptable with a statistically significant correlation between the scores of the French-CPQ8-10 and the evaluation of oral health (r = 0. 381 and p < 0.001) and its impact on oral health quality of life (r = 0.363 and p < 0.001). The loading weights obtained in the Exploratory Factor Analysis showed that this model revealed seven factors with eigenvalue greater than 1, explaining the 63,89% of the cumulative variance. The differences observed between the scores of the study groups revealed good discriminant validity. Criterion validity was supported by significant association between CPQ scores and pain. CONCLUSION: The French-CPQ8-10 is reliable and valid for use with the children of this age group.


Assuntos
Saúde Bucal , Qualidade de Vida , Inquéritos e Questionários/normas , Criança , Fissura Palatina , Comparação Transcultural , Estudos Transversais , Feminino , França , Humanos , Linguagem , Masculino , Percepção , Psicometria , Reprodutibilidade dos Testes , Anormalidades Dentárias , Traduções
7.
Int J Prosthodont ; 31(1): 31­34, 2018 January/February.
Artigo em Inglês | MEDLINE | ID: mdl-29166418

RESUMO

Dental rehabilitation of acute cases of enamel renal syndrome is challenging due to the absence of clinical reports. In the present case history report, examination of an 18-year-old patient revealed a complete lack of permanent teeth, as well as irregular and swollen bone and gingival morphology. Radiographs showed multiple impacted teeth in both arches. Creating a 1.5- to 2-cm interarch space was necessary for setting complete dentures. The ideal occlusal plane was chosen by combining two techniques (cephalometric radiograph and modification of the mandibular occlusal rim according to anatomical guidelines). Extraction of impacted teeth and recontouring of the alveolar process were performed simultaneously. The mandibular denture was connected through Locator abutments to two symphyseal implants. This pioneering clinical report will provide guidance to practitioners in the surgical intervention of patients with FAM20A (family with sequence similarities 20 A) gene mutations.


Assuntos
Amelogênese Imperfeita/reabilitação , Prótese Total , Reabilitação Bucal/métodos , Nefrocalcinose/reabilitação , Adolescente , Amelogênese Imperfeita/diagnóstico por imagem , Humanos , Masculino , Nefrocalcinose/diagnóstico por imagem , Fenótipo
8.
Orphanet J Rare Dis ; 12(1): 94, 2017 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-28526043

RESUMO

BACKGROUND: In the last ten years, national rare disease networks have been established in France, including national centres of expertise and regional ones, with storage of patient data in a bioinformatics tool. The aim was to contribute to the development and evaluation of health strategies to improve the management of patients with rare diseases. The objective of this study has been to provide the first national-level data concerning rare diseases of the head, neck and teeth and to assess the balance between demand and supply of care in France. METHODS: Centres of expertise for rare diseases record a minimum data set on their clinical cases, using a list of rare Head, Neck and Teeth diseases established in 2006. The present analysis focuses on 2008 to 2015 data based on the Orphanet nomenclature. Each rare disease RD "case" was defined by status "affected" and by the degree of diagnostic certainty, encoded as: confirmed, probable or non-classifiable. Analysed parameters, presented with their 95% confidence intervals using a Poisson model, were the following: time and age at diagnosis, proportions of crude and standardized RD prevalence by age, gender and geographical site. The criteria studied were the proportions of patients in Paris Region and the "included cases geography", in which these proportions were projected onto the other French Regions, adjusting for local populations. RESULTS: In Paris Region, estimated prevalence of these diseases was 5.58 per 10,000 inhabitants (95% CI 4.3-7.1). At December 31st 2015, 11,342 patients were referenced in total in France, of whom 7294 were in Paris Region. More than 580 individual clinical entities (ORPHA code) were identified with their respective frequencies. Most abnormalities were diagnosed antenatally. Nearly 80% of patients recorded come to Paris hospitals to obtain either diagnosis, care or follow up. We observed that the rarer the disease, the more patients were referred to Paris hospitals. CONCLUSIONS: A health network covering a range of aspects of the rare diseases problematic from diagnostics to research has been developed in France. Despite this, there is still a noticeable imbalance between health care supply and demand in this area.


Assuntos
Doenças Raras/metabolismo , Feminino , França , Humanos , Masculino , Venenos/metabolismo , Prevalência , Estudos Prospectivos , Doenças Raras/epidemiologia , Doenças Raras/genética , Fatores de Risco
9.
Front Physiol ; 8: 267, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28515694

RESUMO

Background and objective:FAM20A gene mutations result in enamel renal syndrome (ERS) associated with amelogenesis imperfecta (AI), nephrocalcinosis, gingival fibromatosis, and impaired tooth eruption. FAM20A would control the phosphorylation of enamel peptides and thus enamel mineralization. Here, we characterized the structure and chemical composition of unerupted tooth enamel from ERS patients and healthy subjects. Methods: Tooth sections were analyzed by Scanning Electron Microscopy (SEM), Energy Dispersive Spectroscopy (EDS), X-Ray Diffraction (XRD), and X-Ray Fluorescence (XRF). Results: SEM revealed that prisms were restricted to the inner-most enamel zones. The bulk of the mineralized matter covering the crown was formed by layers with varying electron-densities organized into lamellae and micronodules. Tissue porosity progressively increased at the periphery, ending with loose and unfused nanonodules also observed in the adjoining soft tissues. Thus, the enamel layer covering the dentin in all ERS patients (except a limited layer of enamel at the dentino-enamel junction) displayed an ultrastructural globular pattern similar to one observed in ectopic mineralization of soft tissue, notably in the gingiva of Fam20a knockout mice. XRD analysis confirmed the existence of alterations in crystallinity and composition (vs. sound enamel). XRF identified lower levels of calcium and phosphorus in ERS enamel. Finally, EDS confirmed the reduced amount of calcium in ERS enamel, which appeared similar to dentin. Conclusion: This study suggests that, after an initial normal start to amelogenesis, the bulk of the tissue covering coronal dentin would be formed by different mechanisms based on nano- to micro-nodule aggregation. This evocated ectopic mineralization process is known to intervene in several soft tissues in FAM20A gene mutant.

10.
J Med Genet ; 54(1): 26-37, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27530400

RESUMO

BACKGROUND: Amelogenesis imperfecta (AI) is a group of genetic diseases characterised by tooth enamel defects. AI was recently described in patients with familial hypercalciuria and hypomagnesaemia with nephrocalcinosis (FHHNC) caused by CLDN16 mutations. In the kidney, claudin-16 interacts with claudin-19 to control the paracellular passage of calcium and magnesium. FHHNC can be linked to mutations in both genes. Claudin-16 was shown to be expressed during amelogenesis; however, no data are available on claudin-19. Moreover, the enamel phenotype of patients with CLDN19 mutations has never been described. In this study, we describe the clinical and genetic features of nine patients with FHHNC carrying CLDN19 mutations and the claudin-19 expression profile in rat ameloblasts. METHODS: Six FHHNC Brazilian patients were subjected to mutational analysis. Three additional French patients were recruited for orodental characterisation. The expression profile of claudin-19 was evaluated by RT-qPCR and immunofluorescence using enamel epithelium from rat incisors. RESULTS: All patients presented AI at different degrees of severity. Two new likely pathogenic variations in CLDN19 were found: p.Arg200Gln and p.Leu90Arg. RT-qPCR revealed low Cldn19 expression in ameloblasts. Confocal analysis indicated that claudin-19 was immunolocalised at the distal poles of secretory and maturing ameloblasts. CONCLUSIONS: For the first time, it was demonstrated that AI is associated with FHHNC in patients carrying CLDN19 mutations. The data suggest claudin-19 as an additional determinant in enamel formation. Indeed, the coexistence of hypoplastic and hypomineralised AI in the patients was consistent with claudin-19 expression in both secretory and maturation stages. Additional indirect systemic effects cannot be excluded.

11.
J Med Genet ; 53(2): 98-110, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26502894

RESUMO

BACKGROUND: Orodental diseases include several clinically and genetically heterogeneous disorders that can present in isolation or as part of a genetic syndrome. Due to the vast number of genes implicated in these disorders, establishing a molecular diagnosis can be challenging. We aimed to develop a targeted next-generation sequencing (NGS) assay to diagnose mutations and potentially identify novel genes mutated in this group of disorders. METHODS: We designed an NGS gene panel that targets 585 known and candidate genes in orodental disease. We screened a cohort of 101 unrelated patients without a molecular diagnosis referred to the Reference Centre for Oro-Dental Manifestations of Rare Diseases, Strasbourg, France, for a variety of orodental disorders including isolated and syndromic amelogenesis imperfecta (AI), isolated and syndromic selective tooth agenesis (STHAG), isolated and syndromic dentinogenesis imperfecta, isolated dentin dysplasia, otodental dysplasia and primary failure of tooth eruption. RESULTS: We discovered 21 novel pathogenic variants and identified the causative mutation in 39 unrelated patients in known genes (overall diagnostic rate: 39%). Among the largest subcohorts of patients with isolated AI (50 unrelated patients) and isolated STHAG (21 unrelated patients), we had a definitive diagnosis in 14 (27%) and 15 cases (71%), respectively. Surprisingly, COL17A1 mutations accounted for the majority of autosomal-dominant AI cases. CONCLUSIONS: We have developed a novel targeted NGS assay for the efficient molecular diagnosis of a wide variety of orodental diseases. Furthermore, our panel will contribute to better understanding the contribution of these genes to orodental disease. TRIAL REGISTRATION NUMBERS: NCT01746121 and NCT02397824.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala/métodos , Mutação , Anormalidades Dentárias/genética , Amelogênese Imperfeita/genética , Autoantígenos/genética , Deleção Cromossômica , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 11/genética , Estudos de Coortes , Coloboma/genética , Displasia da Dentina/genética , França , Perda Auditiva Neurossensorial/genética , Humanos , Colágenos não Fibrilares/genética , Reprodutibilidade dos Testes
12.
Med Sci (Paris) ; 31(5): 515-21, 2015 May.
Artigo em Francês | MEDLINE | ID: mdl-26059302

RESUMO

Enamel is a unique tissue in vertebrates, acellular, formed on a labile scaffolding matrix and hypermineralized. The ameloblasts are epithelial cells in charge of amelogenesis. They secrete a number of matrix proteins degraded by enzymes during enamel mineralization. This ordered cellular and extracellular events imply that any genetic or environmental perturbation will produce indelible and recognizable defects. The specificity of defects will indicate the affected cellular process. Thus, depending on the specificity of alterations, the teratogenic event can be retrospectively established. Advances in the field allow to use enamel defects as diagnostic tools for molecular disorders. The multifunctionality of enamel peptides is presently identified from their chemical roles in mineralization to cell signaling, constituting a source of concrete innovations in regenerative medicine.


Assuntos
Esmalte Dentário/fisiologia , Ameloblastos/citologia , Ameloblastos/metabolismo , Amelogênese/fisiologia , Animais , Esmalte Dentário/química , Esmalte Dentário/efeitos dos fármacos , Esmalte Dentário/ultraestrutura , Hipoplasia do Esmalte Dentário/genética , Hipoplasia do Esmalte Dentário/fisiopatologia , Proteínas do Esmalte Dentário/fisiologia , Durapatita/química , Órgão do Esmalte/fisiologia , Fluorose Dentária/etiologia , Humanos , Técnicas de Diagnóstico Molecular , Nanosferas , Peptídeo Hidrolases/fisiologia , Teratogênios/farmacologia , Calcificação de Dente/fisiologia
13.
Eur J Hum Genet ; 23(4): 445-51, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25118030

RESUMO

Dentinogenesis imperfecta is an autosomal dominant disease characterized by severe hypomineralization of dentin and altered dentin structure. Dentin extra cellular matrix is composed of 90% of collagen type I and 10% of non-collagenous proteins among which dentin sialoprotein (DSP), dentin glycoprotein (DGP) and dentin phosphoprotein (DPP) are crucial in dentinogenesis. These proteins are encoded by a single gene: dentin sialophosphoprotein (DSPP) and undergo several post-translational modifications such as glycosylation and phosphorylation to contribute and to control mineralization. Human mutations of this DSPP gene are responsible for three isolated dentinal diseases classified by Shield in 1973: type II and III dentinogenesis imperfecta and type II dentin dysplasia. Shield classification was based on clinical phenotypes observed in patient. Genetics results show now that these three diseases are a severity variation of the same pathology. So this review aims to revise and to propose a new classification of the isolated forms of DI to simplify diagnosis for practitioners.


Assuntos
Displasia da Dentina/classificação , Displasia da Dentina/genética , Dentinogênese Imperfeita/classificação , Dentinogênese Imperfeita/genética , Proteínas da Matriz Extracelular/genética , Fosfoproteínas/genética , Sialoglicoproteínas/genética , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Dentina/patologia , Variação Genética , Humanos , Mutação , Fenótipo
14.
Connect Tissue Res ; 55 Suppl 1: 117-20, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25158194

RESUMO

Ameloblastin (AMBN), a member of the enamel matrix protein family, has been recently identified as integral part of the skeleton beyond the enamel. However, the specific role of endogenous AMBN in bone tissue is not fully elucidated. This study aims at investigating mRNA expression of AMBN in wild-type mice in different bone sites from early embryonic to adult stages. AMBN mRNA expression started at pre-dental stages in mouse embryos (E10.5) in both head and body parts. Using laser capture microdissection on 3-day-old mice, we showed an unambiguous mRNA expression of AMBN in extra-dental tissue (mandible bone). Screening of AMBN mRNA expression in adult mice (15-week-old) revealed that mRNA expression of AMBN varied according to the bone site; a higher mRNA levels in mandibular and frontal bone compartments were observed when compared to tibia and occipital bones. These results strongly suggest that AMBN expression may be regulated in a site-specific manner and identify AMBN as a putative in vivo marker of the site-specific fingerprint of bone organs.


Assuntos
Osso e Ossos/metabolismo , Proliferação de Células/fisiologia , Proteínas do Esmalte Dentário/metabolismo , Osteogênese/fisiologia , Animais , Animais Recém-Nascidos , Biomarcadores/análise , Osso e Ossos/citologia , Células Cultivadas , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Camundongos
15.
Int Orthod ; 12(3): 291-302, 2014 Sep.
Artigo em Inglês, Francês | MEDLINE | ID: mdl-25092254

RESUMO

When dental agenesis is encountered, several treatment solutions can be considered: extraction of the primary tooth and closure of the space or, alternatively, conservation of the space with the primary tooth still on the arch until a prosthesis can be placed. In the presence of premolar agenesis, the corresponding primary molar may be infra-occluded relative to the occlusal plane. This situation complicates the treatment plan. Depending on the clinical setting, it can be useful to restore occlusal contacts using composite overlays. We will demonstrate this treatment option via two clinical cases. Tooth conservation helps maintain the bone volume that will later facilitate placement of an implant and limit extrusion of the antagonists as well as tipping of the neighboring teeth.


Assuntos
Anodontia/terapia , Dente Pré-Molar/anormalidades , Má Oclusão/terapia , Dente Molar/patologia , Dente Decíduo/patologia , Perda do Osso Alveolar/prevenção & controle , Criança , Resinas Compostas/química , Implantes Dentários , Materiais Dentários/química , Restauração Dentária Permanente/métodos , Diastema/terapia , Feminino , Humanos , Masculino , Má Oclusão de Angle Classe II/terapia , Mordida Aberta/terapia , Fechamento de Espaço Ortodôntico , Técnica de Expansão Palatina , Planejamento de Assistência ao Paciente , Reabsorção da Raiz/terapia , Mantenedor de Espaço em Ortodontia , Anquilose Dental/complicações , Extração Dentária
16.
PLoS One ; 9(6): e99626, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24933156

RESUMO

Research on enamel matrix proteins (EMPs) is centered on understanding their role in enamel biomineralization and their bioactivity for tissue engineering. While therapeutic application of EMPs has been widely documented, their expression and biological function in non-enamel tissues is unclear. Our first aim was to screen for amelogenin (AMELX) and ameloblastin (AMBN) gene expression in mandibular bones and soft tissues isolated from adult mice (15 weeks old). Using RT-PCR, we showed mRNA expression of AMELX and AMBN in mandibular alveolar and basal bones and, at low levels, in several soft tissues; eyes and ovaries were RNA-positive for AMELX and eyes, tongues and testicles for AMBN. Moreover, in mandibular tissues AMELX and AMBN mRNA levels varied according to two parameters: 1) ontogenic stage (decreasing with age), and 2) tissue-type (e.g. higher level in dental epithelial cells and alveolar bone when compared to basal bone and dental mesenchymal cells in 1 week old mice). In situ hybridization and immunohistodetection were performed in mandibular tissues using AMELX KO mice as controls. We identified AMELX-producing (RNA-positive) cells lining the adjacent alveolar bone and AMBN and AMELX proteins in the microenvironment surrounding EMPs-producing cells. Western blotting of proteins extracted by non-dissociative means revealed that AMELX and AMBN are not exclusive to mineralized matrix; they are present to some degree in a solubilized state in mandibular bone and presumably have some capacity to diffuse. Our data support the notion that AMELX and AMBN may function as growth factor-like molecules solubilized in the aqueous microenvironment. In jaws, they might play some role in bone physiology through autocrine/paracrine pathways, particularly during development and stress-induced remodeling.


Assuntos
Amelogenina/fisiologia , Proteínas do Esmalte Dentário/fisiologia , Mandíbula/metabolismo , Amelogenina/análise , Amelogenina/deficiência , Amelogenina/genética , Animais , Proteínas do Esmalte Dentário/análise , Proteínas do Esmalte Dentário/genética , Difusão , Células Epiteliais/metabolismo , Proteínas do Olho/análise , Proteínas do Olho/fisiologia , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Masculino , Mandíbula/crescimento & desenvolvimento , Mesoderma/metabolismo , Camundongos , Camundongos Knockout , Proteínas Musculares/análise , Proteínas Musculares/fisiologia , Especificidade de Órgãos , Ovário/crescimento & desenvolvimento , Ovário/metabolismo , RNA Mensageiro/análise , RNA Mensageiro/biossíntese , Solubilidade , Testículo/crescimento & desenvolvimento , Testículo/metabolismo , Língua/crescimento & desenvolvimento , Língua/metabolismo , Vísceras/crescimento & desenvolvimento , Vísceras/metabolismo
17.
Orphanet J Rare Dis ; 9: 84, 2014 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-24927635

RESUMO

Amelogenesis imperfecta (AI) is a genetically and clinically heterogeneous group of inherited dental enamel defects. Commonly described as an isolated trait, it may be observed concomitantly with other orodental and/or systemic features such as nephrocalcinosis in Enamel Renal Syndrome (ERS, MIM#204690), or gingival hyperplasia in Amelogenesis Imperfecta and Gingival Fibromatosis Syndrome (AIGFS, MIM#614253). Patients affected by ERS/AIGFS present a distinctive orodental phenotype consisting of generalized hypoplastic AI affecting both the primary and permanent dentition, delayed tooth eruption, pulp stones, hyperplastic dental follicles, and gingival hyperplasia with variable severity and calcified nodules. Renal exam reveals a nephrocalcinosis which is asymptomatic in children affected by ERS. FAM20A recessive mutations are responsible for both syndromes. We suggest that AIGFS and ERS are in fact descriptions of the same syndrome, but that the kidney phenotype has not always been investigated fully in AIGFS. The aim of this review is to highlight the distinctive and specific orodental features of patients with recessive mutations in FAM20A. We propose ERS to be the preferred term for all the phenotypes arising from recessive FAM20A mutations. A differential diagnosis has to be made with other forms of AI, isolated or syndromic, where only a subset of the clinical signs may be shared. When ERS is suspected, the patient should be assessed by a dentist, nephrologist and clinical geneticist. Confirmed cases require long-term follow-up. Management of the orodental aspects can be extremely challenging and requires the input of multi-disciplinary specialized dental team, especially when there are multiple unerupted teeth.


Assuntos
Amelogênese Imperfeita/patologia , Proteínas do Esmalte Dentário/genética , Genes Recessivos , Mutação , Nefrocalcinose/patologia , Anormalidades Dentárias/genética , Amelogênese Imperfeita/genética , Humanos , Nefrocalcinose/genética , Radiografia , Anormalidades Dentárias/diagnóstico por imagem
18.
Front Physiol ; 5: 510, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25601840

RESUMO

While many effectors have been identified in enamel matrix and cells via genetic studies, physiological networks underlying their expression levels and thus the natural spectrum of enamel thickness and degree of mineralization are now just emerging. Several transcription factors are candidates for enamel gene expression regulation and thus the control of enamel quality. Some of these factors, such as MSX2, are mainly confined to the dental epithelium. MSX2 homeoprotein controls several stages of the ameloblast life cycle. This chapter introduces MSX2 and its target genes in the ameloblast and provides an overview of knowledge regarding its effects in vivo in transgenic mouse models. Currently available in vitro data on the role of MSX2 as a transcription factor and its links to other players in ameloblast gene regulation are considered. MSX2 modulations are relevant to the interplay between developmental, hormonal and environmental pathways and in vivo investigations, notably in the rodent incisor, have provided insight into dental physiology. Indeed, in vivo models are particularly promising for investigating enamel formation and MSX2 function in ameloblast cell fate. MSX2 may be central to the temporal-spatial restriction of enamel protein production by the dental epithelium and thus regulation of enamel quality (thickness and mineralization level) under physiological and pathological conditions. Studies on MSX2 show that amelogenesis is not an isolated process but is part of the more general physiology of coordinated dental-bone complex growth.

19.
Am J Pathol ; 183(1): 108-18, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23764278

RESUMO

Endocrine-disrupting chemicals (EDCs), including bisphenol A (BPA), are environmental ubiquitous pollutants and associated with a growing health concern. Anecdotally, molar incisor hypomineralization (MIH) is increasing concurrently with EDC-related conditions, which has led us to investigate the effect of BPA on amelogenesis. Rats were exposed daily to BPA from conception until day 30 or 100. At day 30, BPA-affected enamel exhibited hypomineralization similar to human MIH. Scanning electron microscopy and elemental analysis revealed an abnormal accumulation of organic material in erupted enamel. BPA-affected enamel had an abnormal accumulation of exogenous albumin in the maturation stage. Quantitative real-time PCR, Western blotting, and luciferase reporter assays revealed increased expression of enamelin but decreased expression of kallikrein 4 (protease essential for removing enamel proteins) via transcriptional regulation. Data suggest that BPA exerts its effects on amelogenesis by disrupting normal protein removal from the enamel matrix. Interestingly, in 100-day-old rats, erupting incisor enamel was normal, suggesting amelogenesis is only sensitive to MIH-causing agents during a specific time window during development (as reported for human MIH). The present work documents the first experimental model that replicates MIH and presents BPA as a potential causative agent of MIH. Because human enamel defects are irreversible, MIH may provide an easily accessible marker for reporting early EDC exposure in humans.


Assuntos
Compostos Benzidrílicos/toxicidade , Hipoplasia do Esmalte Dentário/induzido quimicamente , Disruptores Endócrinos/toxicidade , Fenóis/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Amelogênese/efeitos dos fármacos , Animais , Biomarcadores/metabolismo , Western Blotting , Hipoplasia do Esmalte Dentário/metabolismo , Proteínas do Esmalte Dentário/metabolismo , Feminino , Humanos , Calicreínas/metabolismo , Masculino , Microscopia Eletrônica de Varredura , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real
20.
Nephron Physiol ; 122(1-2): 1-6, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23434854

RESUMO

BACKGROUND/AIMS: Calcium homeostasis requires regulated cellular and interstitial systems interacting to modulate the activity and movement of this ion. Disruption of these systems in the kidney results in nephrocalcinosis and nephrolithiasis, important medical problems whose pathogenesis is incompletely understood. METHODS: We investigated 25 patients from 16 families with unexplained nephrocalcinosis and characteristic dental defects (amelogenesis imperfecta, gingival hyperplasia, impaired tooth eruption). To identify the causative gene, we performed genome-wide linkage analysis, exome capture, next-generation sequencing, and Sanger sequencing. RESULTS: All patients had bi-allelic FAM20A mutations segregating with the disease; 20 different mutations were identified. CONCLUSIONS: This autosomal recessive disorder, also known as enamel renal syndrome, of FAM20A causes nephrocalcinosis and amelogenesis imperfecta. We speculate that all individuals with biallelic FAM20A mutations will eventually show nephrocalcinosis.


Assuntos
Amelogênese Imperfeita/genética , Proteínas do Esmalte Dentário/genética , Predisposição Genética para Doença/genética , Mutação , Nefrocalcinose/genética , Adolescente , Adulto , Amelogênese Imperfeita/complicações , Amelogênese Imperfeita/patologia , Criança , Consanguinidade , Exoma/genética , Saúde da Família , Feminino , Genes Recessivos/genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Nefrocalcinose/complicações , Nefrocalcinose/patologia , Linhagem , Análise de Sequência de DNA/métodos , Síndrome , Adulto Jovem
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