RESUMO
Craniofacial microsomia (CFM), also known as the oculo-auriculo-vertebral spectrum, is a congenital disorder characterized by hypoplasia of the mandible and external ear due to tissue malformations originating from the first and second branchial arches. However, distinguishing it from other syndromes of branchial arch abnormalities is difficult, and causal variants remain unidentified in many cases. In this report, we performed an exome sequencing analysis of a Brazilian family with CFM. The proband was a 12-month-old boy with clinical findings consistent with the diagnostic criteria for CFM, including unilateral mandibular hypoplasia, microtia, and external auditory canal abnormalities. A heterozygous de novo nonsense variant (c.713C>G, p.S238*) in PUF60 was identified, which was predicted to be pathogenic in silico. PUF60 has been reported as a causal gene in Verheij syndrome, but not in CFM. Although the boy showed craniofacial abnormalities and developmental delay that overlapped with Verheij syndrome, the facial asymmetry with unilateral hypoplasia of the mandible observed in this case did not match the previously reported phenotypes of PUF60 variants. Our findings expand the phenotypic range of PUF60 variants that cover CFM and Verheij syndrome.
Assuntos
Síndrome de Goldenhar , Fenótipo , Humanos , Masculino , Síndrome de Goldenhar/genética , Síndrome de Goldenhar/patologia , Síndrome de Goldenhar/diagnóstico , Lactente , Fatores de Processamento de RNA/genética , Proteínas Repressoras/genética , Sequenciamento do Exoma , Mandíbula/anormalidades , Mandíbula/patologia , Linhagem , Códon sem Sentido/genéticaRESUMO
BACKGROUND: Poverty negatively impacts beneficial aspects of mental development, such as resilience. Toothbrushing, an oral health behavior, has the potential to protect children's resilience through its anti-inflammatory and self-management effects and may be more effective for children, especially children in poverty. This study investigated whether toothbrushing boosts resilience among children, especially children under poverty, and modifies the association between poverty and resilience using a longitudinal population sample of school children. METHODS: Data from the Adachi Child Health Impact of Living Difficulty (A-CHILD Study) were analyzed. A baseline study was conducted in 2015 in which the children were in first grade and followed through fourth grade (N = 3459, response rate: 80%, follow-up rate: 82%). Poverty was assessed by material deprivation (life-related deprivation and child-related deprivation) and annual household income at baseline. Children's toothbrushing frequency was assessed at baseline and classified into less than twice a day or twice or more a day. Children's resilience was assessed at baseline and follow-up using the Children's Resilient Coping Scale (range 0-100). RESULTS: Children who brushed their teeth twice or more a day in first grade had 3.50 points greater resilience scores in fourth grade than those who brushed their teeth less than twice a day in first grade. After adjusting for confounders, including resilience in first grade, among underpoverty children, those who brushed their teeth twice or more a day in first grade had higher resilience scores [2.66 (95% CI = 0.53, 4.79)] than those who brushed their teeth less than twice a day. Among nonpoverished children, toothbrushing frequency in first grade did not significantly correlate with resilience in fourth grade. CONCLUSIONS: The beneficial effect of toothbrushing twice or more a day on resilience was more significant among children in poverty than among those without poverty in elementary school in Japan. Health policy focused on frequent toothbrushing may contribute to boosting resilience among children living in poverty.
Assuntos
Pobreza , Resiliência Psicológica , Escovação Dentária , Humanos , Escovação Dentária/estatística & dados numéricos , Criança , Estudos Longitudinais , Feminino , MasculinoRESUMO
Tooth agenesis is one of the most frequent congenital abnormalities found in the maxillofacial region. Oligodontia, a severe form of tooth agenesis, occurs as an isolated anomaly or as a syndromic feature. We performed whole exome sequencing analyses to identify causative mutation in a Japanese family with three affected individuals with non-syndromic oligodontia. After variant filtering procedures and validation by Sanger sequencing, we identified one missense mutation (c.668 C > T, p.Gly223Asp) in OPN3 at 1q43, encoding a photosensitive G-protein-coupled receptor (GPCR) expressed in various tissues including brain, liver, and adipose. This mutation was predicted to be pathogenic in silico and was not found in the public databases. We further examined 48 genetically unrelated cases by targeted sequencing of the OPN3 gene region and found one additional missense variant in this gene (c.768 C > T, p.Met256Ile) that was also predicted to be pathogenic. Localization of OPN3 protein by immunohistochemical analysis using mouse embryo revealed its specific expression in the tooth gems from bud to bell stages and their surrounding tissues. These results indicated that OPN3 was involved in non-syndromic oligodontia, which has made an anchoring point for clinical application including DNA diagnostics.
Assuntos
Anodontia/genética , Anodontia/metabolismo , Predisposição Genética para Doença , Opsinas de Bastonetes/genética , Opsinas de Bastonetes/metabolismo , Animais , Humanos , Japão , Camundongos , Mutação de Sentido Incorreto , Linhagem , Fenótipo , Análise de Sequência , Sequenciamento do ExomaRESUMO
Extracellular vesicles (EVs) have emerged as important targets in biological and medical studies because they are involved in diverse human diseases and bacterial pathogenesis. Although antibodies targeting the surface biomarkers are widely used to detect EVs, peptide-based curvature sensors are currently attracting an attention as a novel tool for marker-free EV detection techniques. We have previously created a curvature-sensing peptide, FAAV and applied it to develop a simple and rapid method for detection of bacterial EVs in cultured media. The method utilized the fluorescence/Förster resonance energy transfer (FRET) phenomenon to achieve the high sensitivity to changes in the EV amount. In the present study, to develop a practical and easy-to-use approach that can detect bacterial EVs by peptides alone, we designed novel curvature-sensing peptides, N-terminus-substituted FAAV (nFAAV) peptides. The nFAAV peptides exerted higher α-helix-stabilizing effects than FAAV upon binding to vesicles while maintaining a random coil structure in aqueous solution. One of the nFAAV peptides showed a superior binding affinity for bacterial EVs and detected changes in the EV amount with 5-fold higher sensitivity than FAAV even in the presence of the EV-secretory bacterial cells. We named nFAAV5, which exhibited the high ability to detect bacterial EVs, as an EV-sensing peptide. Our finding is that the coil-α-helix structural transition of the nFAAV peptides serve as a key structural factor for highly sensitive detection of bacterial EVs.
Assuntos
Vesículas Extracelulares/química , Peptídeos/química , 4-Cloro-7-nitrobenzofurazano , Sequência de Aminoácidos , Basidiomycota/química , Técnicas Biossensoriais , Vesículas Extracelulares/ultraestrutura , Transferência Ressonante de Energia de Fluorescência , Cinética , Lipossomos/química , Conformação ProteicaRESUMO
Klippel-Trenaunay syndrome (KTS) is a congenital disorder associated with capillary, venous, lymphatic vascular malformations, and unilateral hypertrophy of the soft tissue and bone. We report a case of a 5-year-old girl with KTS who was followed up until age 17. The asymmetry of her maxillary dentition became remarkable with growth, although no significant left-right difference in either the maxilla or mandible was recognized. Acceptable occlusion was achieved without fixed orthodontic appliances; however, it was necessary to develop treatment plans in accordance with the general symptoms of the disease.
Assuntos
Síndrome de Klippel-Trenaunay-Weber , Pré-Escolar , Feminino , Humanos , Síndrome de Klippel-Trenaunay-Weber/diagnóstico por imagem , Síndrome de Klippel-Trenaunay-Weber/terapia , Mandíbula/diagnóstico por imagem , PacientesRESUMO
Mutations in the gene encoding BCL-6 corepressor (BCOR) are responsible for oculofaciocardiodental (OFCD) syndrome, which is a rare X-linked dominant disorder characterized by radiculomegaly of permanent teeth as the most typical symptom. To function as a transcriptional corepressor, BCOR needs to enter the nucleus; however, the molecular pathway for its nuclear translocation during dental root formation remains unclear. The purpose of this study was to determine the mechanism underlying BCOR transport into the nucleus. Our results showed that human periodontal ligament (PDL) cells expressed karyopherin α (KPNA)2, KPNA4, and KPNA6 belonging to a family of nuclear import proteins, which interacted with BCOR in the immunoprecipitation assay. Site-directed mutagenesis targeting the two nuclear localization signals (NLSs) within BCOR reduced its nuclear translocation; however, co-expression of KPNA2, KPNA4, or KPNA6 with BCOR carrying a previously described mutation which eliminated one of the two NLSs significantly increased nuclear accumulation of the mutant BCOR, indicating participation of KPNA in BCOR nuclear translocation. Comparative expression profiling of PDL cells isolated from normal and OFCD patients revealed significant downregulation of SMAD4, GLI1, and nuclear factor 1-C (NFIC) mRNA expression, suggesting that BCOR mutations cause hyperactive root formation in OFCD syndrome by inhibiting SMAD4-Hedgehog-NFIC signaling implicated in dental root development. Our study contributes to understanding of the mechanisms providing nuclear import of BCOR during root formation.
Assuntos
Núcleo Celular/metabolismo , Ligamento Periodontal/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Repressoras/metabolismo , alfa Carioferinas/metabolismo , Transporte Ativo do Núcleo Celular , Adolescente , Adulto , Sequência de Aminoácidos , Substituição de Aminoácidos , Animais , Células COS , Criança , Chlorocebus aethiops , Regulação para Baixo/genética , Humanos , Masculino , Proteínas Mutantes/metabolismo , Mutação/genética , Sinais de Localização Nuclear/metabolismo , Ligação Proteica , Proteínas Proto-Oncogênicas/química , Proteínas Proto-Oncogênicas/genética , Proteínas Repressoras/química , Proteínas Repressoras/genética , Frações Subcelulares/metabolismo , Transcrição Gênica , beta Carioferinas/metabolismoRESUMO
OBJECTIVE: Maxillary distraction osteogenesis (DO) is a mainstream surgical technique for patients who have severe maxillary hypoplasia associated with craniofacial syndromes and cleft-related deformities. However, limited information about the biomechanical aspects of maxillary DO is available limiting broad utilization and improvements to the procedure. The objective of this study was to analyze force levels during the active distraction process and to investigate the relationship between distraction force and maxillary movement during Le Fort I maxillary DO using a rigid external distraction (RED) system. PATIENTS: Microtension gauges were integrated into the distraction wires on each side of the RED system. Six patients with cleft lip and palate aged 12.8 to 23.5 years underwent strain gauge measurements during maxillary advancement with DO using an RED system. Lateral cephalograms were taken to measure maxillary horizontal, vertical, and linear movements after DO. RESULTS: The average linear maxillary movement was 11.2âmm (range 8.5-15.9âmm). The applied forces ranged from 13.4 to 26.8âN. The distance of maxillary movement was proportional to the distraction force. CONCLUSIONS: The measurement of distraction forces during DO provides important information with which to establish appropriate protocols. Patients requiring more advancement may require more distraction force. However, other factors such as scarring, patient anatomy, surgical freedom of the osteotomized maxilla, and the like, may affect the required force during DO with the RED system.
Assuntos
Fissura Palatina , Maxila , Osteogênese por Distração , Osteotomia de Le Fort/métodos , Complicações Pós-Operatórias/prevenção & controle , Adolescente , Cefalometria/métodos , Fenda Labial/cirurgia , Fissura Palatina/diagnóstico , Fissura Palatina/fisiopatologia , Fissura Palatina/cirurgia , Feminino , Humanos , Masculino , Maxila/crescimento & desenvolvimento , Maxila/cirurgia , Osteogênese por Distração/efeitos adversos , Osteogênese por Distração/instrumentação , Osteogênese por Distração/métodos , Radiografia/métodos , Resultado do Tratamento , Adulto JovemRESUMO
Marfan syndrome (MFS) is caused by abnormal systemic connective tissue. The main clinical manifestations include long limbs, long slender fingers, lens subluxation, abnormal cardiac valves, and aortic aneurysm. We report the case of an 11-year-old patient with MFS who underwent orthodontic treatment and was followed up until the age of 25 years. We found no significant differences in tooth movement between the patient with MFS and healthy subjects. However, because patients with MFS show characteristic facial growth and an increased risk of developing systemic comorbidities, their dental status requires careful observation over time.
Assuntos
Má Oclusão Classe III de Angle/terapia , Síndrome de Marfan/complicações , Ortodontia Corretiva/métodos , Cefalometria , Criança , Humanos , Masculino , Má Oclusão Classe III de Angle/diagnóstico por imagem , Radiografia PanorâmicaRESUMO
OBJECTIVE: The aim of this case study was to provide a detailed report of the orthodontic approach used in treating a Japanese patient with congenital hypoglossia. PATIENT: The patient was a 6-year-old girl with hypoglossia, micrognathia, congenital absence of three incisors, and a telescopic occlusion accompanied by an extremely narrow lower arch. She had no limb anomalies, and her speech was normal. RESULTS: Bite opening and mandibular widening from the early mixed dentition dramatically improved the extremely constricted mandible and telescopic occlusion. Cephalometric tracings taken from the beginning to the end of active treatment revealed substantial forward and downward growth in the mandible over time, which may have contributed to correction of the intermaxillary relationship. CONCLUSIONS: Treatment of telescopic occlusion by bite opening and mandibular widening from the early mixed dentition may be effective in facilitating mandibular growth acceleration. An acceptable intermaxillary occlusal relationship and improvement of profile were achieved by an orthodontic approach in this case.
Assuntos
Desenvolvimento Maxilofacial , Micrognatismo/terapia , Ortodontia Corretiva/métodos , Língua/anormalidades , Anormalidades Múltiplas , Cefalometria , Criança , Dentição Mista , Feminino , Humanos , Japão , Mandíbula/anormalidades , Mandíbula/crescimento & desenvolvimentoRESUMO
Oculofaciocardiodental (OFCD) syndrome is a rare X-linked dominant condition. Mutations in BCOR have been described as causal in OFCD syndrome. Almost all BCOR mutations result in premature termination codons (PTCs); therefore, nonsense-mediated mRNA decay (NMD) might have an important role in pathogenesis. The purpose of this study was to identify BCOR mutations in two OFCD patients, if it present, and to clarify the pathogenesis of radiculomegaly using one OFCD patient's pulp and periodontal ligament (PDL) cells. In our genetic analysis, two novel BCOR mutations were found. We also examined the transcript levels and the effects of NMD using cultured pulp and PDL cells from one affected patient. BCOR expression was normal in pulp but reduced in PDL cells, which is consistent with the higher rates of NMD in PDL cells. The mutant PDL cells had unstable mutant transcripts and proliferated faster than did wild-type cells, but mutant pulp cells appeared normal by these measures. In summary, the nonsense and frameshift mutations, which introduce PTCs, were found to contribute to OFCD syndrome in our two patients. Furthermore, in PDL cells, the mutation resulting in a PTC corresponded to greater NMD, unstable mutant transcripts and increased cell proliferation, which may contribute to hyperactive root formation.
Assuntos
Catarata/congênito , Códon sem Sentido , Polpa Dentária/metabolismo , Defeitos dos Septos Cardíacos/genética , Microftalmia/genética , Ligamento Periodontal/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Repressoras/genética , Adolescente , Adulto , Catarata/genética , Catarata/metabolismo , Catarata/patologia , Proliferação de Células , Células Cultivadas , Polpa Dentária/patologia , Feminino , Defeitos dos Septos Cardíacos/metabolismo , Defeitos dos Septos Cardíacos/patologia , Humanos , Microftalmia/metabolismo , Microftalmia/patologia , Degradação do RNAm Mediada por Códon sem Sentido , Ligamento Periodontal/patologia , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Repressoras/metabolismoRESUMO
OBJECTIVES: Oculo-facio-cardio-dental (OFCD) syndrome is a rare X-linked genetic disorder caused by mutations in the BCL6 co-repressor (BCOR) and is mainly characterized by radiculomegaly (elongated dental roots). All BCOR mutations reported to date have been associated with premature termination codons, indicating that nonsense-mediated mRNA decay (NMD) might play a vital role in the pathogenesis of OFCD syndrome. However, the molecular mechanisms underlying NMD remain unclear. In this study, we investigated the involvement of up-frameshift protein 1 (UPF1), which plays a central role in NMD, in the hyperactive root formation caused by BCOR mutations. METHODS: Periodontal ligament cells, isolated from a Japanese woman with a c.3668delC frameshift mutation in BCOR, and primary human periodontal ligament fibroblasts (HPdLFs) were used for an RNA immunoprecipitation assay to confirm the binding of UPF1 to mutated BCOR. Additionally, the effects of UPF1 on the BCOR transcription levels and corresponding gene expression were determined by performing relative quantitative real-time polymerase chain reactions. RESULTS: RNA immunoprecipitation revealed that UPF1 binds to exon 9 of mutated BCOR. Additionally, UPF1 knockdown via siRNA upregulated the transcription of BCOR, whereas overexpression of wild-type and mutated BCOR with the same frameshift mutation in HPdLFs altered bone morphogenetic protein 2 (BMP2) expression. CONCLUSIONS: Our findings indicate that BCOR mutations regulate the transcription of BCOR via UPF1, which may in turn regulate the expression of BMP2. NMD, caused by a c.3668delC mutation, potentially leads to an OFCD syndrome phenotype, including elongated dental roots.
Assuntos
Catarata/congênito , Mutação da Fase de Leitura , Defeitos dos Septos Cardíacos , Microftalmia , Degradação do RNAm Mediada por Códon sem Sentido , Feminino , Humanos , Mutação da Fase de Leitura/genética , Degradação do RNAm Mediada por Códon sem Sentido/genética , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Códon sem Sentido/genética , Transativadores/genética , Transativadores/metabolismo , RNA Helicases/genética , RNA Helicases/metabolismoRESUMO
Short stature in children is a marker of low nutritional status and has been suggested to be associated with dental caries. However, longitudinal studies on this topic are scarce. Data from a longitudinal study of elementary school children in Adachi City, Tokyo, Japan, were analyzed. In 2015, caregivers of children at grade 1 answered questionnaires, and information on dental caries and height measured at school health checkups was merged and followed to grade 6 (N = 3576; follow up rate = 83.3%). The association between short stature at grade 1 (-2.01 standard deviation (SD)--3.00 SD, or <-3.00 SD in height-for-age according to the World Health Organization criteria) and the number of decayed, missing, or filled permanent teeth (DMFT) at grade 6 was examined using multivariable Poisson regression with robust standard error. After adjusting for confounders, children with a short stature at grade 1 had a higher DMFT number at grade 6: the mean ratios (95% confidence interval) were 1.17 (0.89-1.54) and 2.18 (1.03-4.64) for children with a height-for-age -2.01 SD--3.00 SD, and those with a height-for-age < -3.00, respectively. Short stature at grade 1 could be a marker of future dental caries in the permanent teeth at grade 6.
Assuntos
Cárie Dentária , Criança , Humanos , Pré-Escolar , Japão/epidemiologia , Estudos de Coortes , Cárie Dentária/epidemiologia , Suscetibilidade à Cárie Dentária , Estudos LongitudinaisRESUMO
Objective : To evaluate the long-term maxillomandibular changes after maxillary distraction osteogenesis in growing children having cleft lip with or without cleft palate. Patients : Eight Japanese patients with cleft lip with or without cleft palate aged 9.3 to 13.1 years. Measures : The maxillary and mandibular positions before (T0), immediately after (T1), and 1, 3, and 5 years after distraction osteogenesis (T2, T3, and T4, respectively) measured on cephalograms superimposed at the sella turcica with the Frankfort horizontal plane as the horizontal reference. The anterior nasal spine (x, y), pogonion (x), and menton (y) were used for linear measurements, and sella turcica-nasion-point A, sella turcica-nasion-point B, and point A-nasion-point B angles were used for angular measurements. Results : The mean horizontal maxillary advancement (anterior nasal spine [x]) was 12.3 mm during T0 to T1, but -2.7, -1.1, and -0.1 mm of the posttreatment changes were observed during T1 to T2, T2 to T3, and T3 to T4, respectively. Anterior nasal spine (y) shifted 2.3 mm downward during T0 to T1, and further downward changes were observed during T1 to T2 and T2 to T3 (P < .05). Pogonion (x) did not show distinct changes due to individual variance, but menton (y) shifted downward from T1 to T4. Sella turcica-nasion-point A significantly decreased during T1 to T2 and T2 to T3 but not during T3-T4. Point A-nasion-point B significantly decreased only during T2 to T3, and sella turcica-nasion-point B did not show any distinct change. Conclusions : There was no further maxillary advancement after distraction osteogenesis in the growing children with cleft lip with or without cleft palate. Therefore, long-term observation and management of occlusion in case of the mandibular growth pattern are important.
Assuntos
Fenda Labial , Osteogênese por Distração , Cefalometria , Criança , Humanos , Osteotomia de Le FortRESUMO
Objective : Ectrodactyly-ectodermal dysplasia-clefting syndrome is a congenital anomaly characterized by ectodermal dysplasia, ectrodactyly, cleft lip and palate, and lacrimal duct anomalies. Because this syndrome is frequently accompanied by a congenital lack of teeth, narrow palate, and malocclusion, comprehensive orthodontic intervention is required. Design : To highlight the specific dental and maxillofacial characteristics of ectrodactyly-ectodermal dysplasia-clefting syndrome, six Japanese individuals diagnosed with the syndrome are described here. Patients : The subjects consisted of two boys and four girls (age range, 6.0 to 13.9 years) diagnosed with ectrodactyly-ectodermal dysplasia-clefting syndrome by medical and dental specialists. Their conditions included ectodermal dysplasia (hypodontia, microdontia, enamel hypoplasia, and abnormalities in hair and nails), cleft lip and/or palate, and ectrodactyly. Cephalograms, panoramic x-rays, and dental casts were taken; systemic complications were recorded at the first visit to our dental hospital. Results : All individuals had severe oligodontia with 9 to 18 missing teeth. The missing teeth were mainly maxillary and mandibular incisors and second bicuspids, arranged in a symmetrical manner. Cephalometric analysis showed retruded and short maxilla due to cleft lip and/or palate. It is interesting that all individuals showed a characteristically shaped mandibular symphysis with a retruded point B. It is likely that this unusual symphyseal morphology is due to the lack of mandibular incisors. Conclusions : This study demonstrates the presence of severe oligodontia in the incisal and premolar regions and describes a characteristic maxillary and mandibular structure in Japanese individuals with ectrodactyly-ectodermal dysplasia-clefting syndrome.
Assuntos
Anodontia , Displasia Ectodérmica , Cefalometria , Humanos , SíndromeRESUMO
This study investigates rhythmic jaw movement (RJM) patterns and masticatory muscle activities during electrical stimulation in two cortical masticatory areas in obese male Zucker rats (OZRs), compared to their counterparts-lean male Zucker rats (LZRs) (seven each). At the age of 10 weeks, electromyographic (EMG) activity of the right anterior digastric muscle (RAD) and masseter muscles, and RJMs were recorded during repetitive intracortical micro-stimulation in the left anterior and posterior parts of the cortical masticatory area (A-area and P-area, respectively). Only P-area-elicited RJMs, which showed a more lateral shift and slower jaw-opening pattern than A-area-elicited RJMs, were affected by obesity. During P-area stimulation, the jaw-opening duration was significantly shorter (p < 0.01) in OZRs (24.3 ms) than LZRs (27.9 ms), the jaw-opening speed was significantly faster (p < 0.05) in OZRs (67.5 mm/s) than LZRs (50.8 mm/s), and the RAD EMG duration was significantly shorter (p < 0.01) in OZRs (5.2 ms) than LZR (6.9 ms). The two groups had no significant difference in the EMG peak-to-peak amplitude and EMG frequency parameters. This study shows that obesity affects the coordinated movement of masticatory components during cortical stimulation. While other factors may be involved, functional change in digastric muscle is partly involved in the mechanism.
RESUMO
Mutations in the B-cell lymphoma 6 (BCL6) interacting corepressor (BCOR) cause oculo-facio-cardio-dental (OFCD) syndrome, a rare X-linked dominant condition that includes dental radiculomegaly among other characteristics. BCOR regulates downstream genes via BCL6 as a transcriptional corepressor. However, the molecular mechanism underlying the occurrence of radiculomegaly is still unknown. Thus, this study was aimed at identifying BCOR-regulated genetic pathways in radiculomegaly. The microarray profile of affected tissues revealed that the gene-specific transcriptional factors group, wherein nucleus factor 1B, distal-less homeobox 5, and zinc finger protein multitype 2 (ZFPM2) were the most upregulated, was significantly expressed in periodontal ligament (PDL) cells of the diseased patient with a frameshift mutation (c.3668delC) in BCOR. Wild-type BCOR overexpression in human periodontal ligament fibroblasts cells significantly hampered cellular proliferation and ZFPM2 mRNA downregulation. Promoter binding assays showed that wild-type BCOR was recruited in the BCL6 binding of the ZFPM2 promoter region after immunoprecipitation, while mutant BCOR, which was the same genotype as of our patient, failed to recruit these promoter regions. Knockdown of ZFPM2 expression in mutant PDL cells significantly reduced cellular proliferation as well as mRNA expression of alkaline phosphatase, an important marker of odontoblasts and cementoblasts. Collectively, our findings suggest that BCOR mutation-induced ZFPM2 regulation via BCL6 possibly contributes to hyperactive root formation in OFCD syndrome. Clinical data from patients with rare genetic diseases may aid in furthering the understanding of the mechanism controlling the final root length.
RESUMO
(1) This study aimed to investigate the association between child abuse and oral habits in adolescents in Mongolia. (2) A cross-sectional survey was conducted with children and their caregivers in Ulaanbaatar, Mongolia. Parents of 770 children enrolled in two public schools in Ulaanbaatar, Mongolia, completed questionnaires regarding the physical and psychological abuse that their children were subjected to and the presence of poor oral habits (biting nails/lips/pens and bruxism). Multivariable Poisson regression models were fitted with adjustment for age, gender, age of the mother, parental education, family income level, birth order, and living status with grandparents. (3) Biting nails/lips/pens and bruxism were reported by 39.0% and 17.5% of the respondents, respectively. Biting nails/lips/pens was significantly associated with physical abuse but was not significantly associated with psychological abuse (prevalence ratio, PR [95% confidence interval, CI]: 1.44 [1.07-1.95] and 1.34 [0.98-1.83], respectively). However, bruxism was not associated with physical or psychological abuse (PR [95% CI]: 1.16 [0.77-1.77] and 1.04 [0.68-1.61], respectively). (4) Child abuse was associated with biting habits among Mongolian adolescents.
Assuntos
Bruxismo , Maus-Tratos Infantis , Adolescente , Criança , Estudos Transversais , Feminino , Hábitos , Humanos , Mães , Prevalência , Inquéritos e QuestionáriosRESUMO
Mutations in the paired-domain transcription factor PAX9 are associated with non-syndromic tooth agenesis that preferentially affects posterior dentition. Of the 18 mutations identified to date, eight are phenotypically well-characterized missense mutations within the DNA-binding paired domain. We determined the structural and functional consequences of these paired domain missense mutations and correlated our findings with the associated dental phenotype variations. In vitro testing included subcellular localization, protein-protein interactions between MSX1 and mutant PAX9 proteins, binding of PAX9 mutants to a DNA consensus site and transcriptional activation from the Pax9 effector promoters Bmp4 and Msx1 with and without MSX1 as co-activator. All mutant PAX9 proteins were localized in the nucleus of transfected cells and physically interacted with MSX1 protein. Three of the mutants retained the ability to bind the consensus paired domain recognition sequence; the others were unable or only partly able to interact with this DNA fragment and also showed a similarly impaired capability for activation of transcription from the Msx1 and Bmp4 promoters. For seven of the eight mutants, the degree of loss of DNA-binding and promoter activation correlated quite well with the severity of the tooth agenesis pattern seen in vivo. One of the mutants however showed neither reduction in DNA-binding nor decrease in transactivation; instead, a loss of responsiveness to synergism with MSX1 in target promoter activation and a dominant negative effect when expressed together with wild-type PAX9 could be observed. Our structure-based studies, which modeled DNA binding and subdomain stability, were able to predict functional consequences quite reliably.
Assuntos
Mutação , Fator de Transcrição PAX9/química , Fator de Transcrição PAX9/genética , Dente/crescimento & desenvolvimento , Dente/patologia , Sequência de Aminoácidos , Animais , Sítios de Ligação , Proteína Morfogenética Óssea 4/genética , Proteína Morfogenética Óssea 4/metabolismo , Células COS , Chlorocebus aethiops , Humanos , Fator de Transcrição MSX1/genética , Fator de Transcrição MSX1/metabolismo , Camundongos , Dados de Sequência Molecular , Fator de Transcrição PAX9/metabolismo , Regiões Promotoras Genéticas , Ligação Proteica , Estrutura Terciária de Proteína , Alinhamento de Sequência , Dente/química , Dente/metabolismo , Ativação TranscricionalRESUMO
INTRODUCTION: Beckwith-Wiedemann syndrome (BWS) is a genetic disorder characterized by exomphalos, macroglossia and gigantism. Previous studies reported a wide variation in the skeletal and occlusal characteristics in individuals affected by BWS. However, these studies were performed by analyzing both individuals who had and those had not received a glossectomy, which has a high impact on the jaw growth and occlusion. To highlight the intrinsic characteristics of BWS, 7 Japanese affected individuals without glossectomy were analyzed in this study. METHODS: Seven individuals who had been diagnosed with BWS by medical specialists and had not undergone glossectomy were analyzed. Cephalograms and dental casts were taken and systemic complications were recorded at the first visit. RESULTS: Individuals uniformly showed a higher birth height and weight, macroglossia, large anterior cranial base, and mandibular body. They exhibited a wide dental arch and an anterior open bite due to the undererupted and proclined anterior teeth. A wide variation was seen in the gonial angle, but the facial height was large overall. CONCLUSIONS: As intrinsic characteristics of BWS, individuals exhibited macroglossia resulting in an anterior open bite and a wide dental arch. A long facial height and an enlarged anterior cranial base and mandibular body were also noted.
Assuntos
Síndrome de Beckwith-Wiedemann/patologia , Face , Ossos Faciais/patologia , Má Oclusão/patologia , Peso ao Nascer , Estatura , Cefalometria , Criança , Pré-Escolar , Dente Canino/patologia , Arco Dental/patologia , Ossos Faciais/crescimento & desenvolvimento , Feminino , Glossectomia , Humanos , Incisivo/patologia , Macroglossia/patologia , Masculino , Mandíbula/patologia , Modelos Dentários , Mordida Aberta/patologia , Prognatismo/patologia , Base do Crânio/patologiaRESUMO
The effect of altered occlusal force on masticatory-related neuromuscular control, which projects from the anterior part of the cortical masticatory area (A-CMA), during growth remains unclear. This study sought to evaluate the effect of occlusal hypofunction on neuromuscular development of jaw muscle activities and cortically-induced rhythmic jaw movements (RJMs) in growing rats. Sixty-four 2-week-old male albino Wistar rats were divided into the control (fed normal diet) and experimental (fed soft diet) groups soon after weaning. Electromyographic activity was recorded at 5, 7, 9, and 11 weeks from the right masseter and anterior digastric along with RJMs. We found a significantly longer onset latency and smaller peak-to-peak amplitude in the experimental group than that in the control group. The RJMs showed an increase in gape size and lateral excursion until up to 9 weeks in both groups. However, both the average gape size and lateral excursion were significantly smaller in the experimental group than that in the control group after 9 weeks. The jaw movement pattern also showed a significant decrease at the maximum opening period in the experimental group. Our findings indicate that inadequate occlusal function during growth alters neuromuscular control of masticatory behaviors and impairs the pattern of RJMs.