RESUMO
The objective was to study the morphology of the articular disc and analyse the immunohistochemical expression of types I and III collagen markers in the temporomandibular joint (TMJ) disc of human foetuses of different gestational ages. Twenty TMJ from human foetuses supplied by Universidade Federal de Uberaba with gestational ages from 17 to 24 weeks were studied. The gestational age of the foetuses was determined by measuring the crown-rump (CR) length. Macroscopically, the foetuses were fixed in 10% formalin solution and dissected by removing the skin and subcutaneous tissue and exposing the deep structures. Immunohistochemical markers of type I and III were used to characterize the existence of collagen fibres. Analysis of the immunohistochemical markers of types I and III collagen revealed the presence of heterotypical fibril networks.
Assuntos
Colágeno Tipo II/biossíntese , Colágeno Tipo I/biossíntese , Feto/embriologia , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Disco da Articulação Temporomandibular/embriologia , Feminino , Feto/citologia , Idade Gestacional , Humanos , Imuno-Histoquímica , Masculino , Disco da Articulação Temporomandibular/citologiaRESUMO
The purpose of this study was to evaluate hard palate asymmetry during development. The palates of 248 dry skulls were photographed and evaluated digitally. The skulls were divided into seven groups: fetus, newborn, infant, child, adolescent, adult, and aged. Linear measures were obtained from great palatine foramen (GPF) to incisive fossa (INC) and to posterior nasal spine (PNS). Angular measures were obtained from the former landmarks plus the point on sutures intersection between maxillary and palatine bones. Asymmetry was evaluated intra and intergroups. All skulls showed some degree of right-left asymmetry in the hard palate. Regardless of hard palate asymmetry, none of the right-left side differences was statistically significant. For the intergroups assessment, none of the asymmetry index means were statistically different. The posterior part of palate (PNS x GPF) measures was more asymmetric than the anterior part (INC x GPF), showing, respectively, 4.6% and 2.8% of mean asymmetry index. Angular measures showed a more symmetric behavior than the linear ones. Hard palate asymmetry occurs even in the absence of masticatory function, showing that this feature begins early in fetal life and persists through development.
Assuntos
Feto/anatomia & histologia , Palato/anatomia & histologia , Palato/crescimento & desenvolvimento , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Dissecação , Feminino , Desenvolvimento Humano , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Palato/embriologia , Caracteres SexuaisRESUMO
We present the first comprehensive study, to our knowledge, on genomic chromosomal analysis in syndromic craniosynostosis. In total, 45 patients with craniosynostotic disorders were screened with a variety of methods including conventional karyotype, microsatellite segregation analysis, subtelomeric multiplex ligation-dependent probe amplification) and whole-genome array-based comparative genome hybridisation. Causative abnormalities were present in 42.2% (19/45) of the samples, and 27.8% (10/36) of the patients with normal conventional karyotype carried submicroscopic imbalances. Our results include a wide variety of imbalances and point to novel chromosomal regions associated with craniosynostosis. The high incidence of pure duplications or trisomies suggests that these are important mechanisms in craniosynostosis, particularly in cases involving the metopic suture.
Assuntos
Aberrações Cromossômicas , Segregação de Cromossomos , Craniossinostoses/genética , Repetições de Microssatélites , Humanos , Cariotipagem , Hibridização de Ácido Nucleico/métodos , Polimorfismo GenéticoRESUMO
Trigonocephaly is a rare form of craniosynostosis characterized by the premature closure of the metopic suture. To contribute to a better understanding of the genetic basis of metopic synostosis and in an attempt to restrict the candidate regions related to metopic suture fusion, we studied 76 unrelated patients with syndromic and non-syndromic trigonocephaly. We found a larger proportion of syndromic cases in our population and the ratio of affected male to female was 1.8 : 1 and 5 : 1 in the non-syndromic and syndromic groups, respectively. A microdeletion screening at 9p22-p24 and 11q23-q24 was carried out for all patients and deletions in seven of them were detected, corresponding to 19.4% of all syndromic cases. Deletions were not found in non-syndromic patients. We suggest that a molecular screening for microdeletions at 9p22-p24 and 11q23-q24 should be offered to all syndromic cases with an apparently normal karyotype because it can potentially elucidate the cause of trigonocephaly in this subset of patients. We also suggest that genes on the X-chromosome play a major role in syndromic trigonocephaly.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 9 , Craniossinostoses/genética , Testes Genéticos/métodos , Criança , Pré-Escolar , Estudos de Coortes , Craniossinostoses/diagnóstico , Feminino , Humanos , Lactente , Cariotipagem , Masculino , Linhagem , FenótipoRESUMO
Twenty-eight families with a clinical diagnosis of Treacher Collins syndrome were screened for mutations in the 25 coding exons of TCOF1 and their adjacent splice junctions through SSCP and direct sequencing. Pathogenic mutations were detected in 26 patients, yielding the highest detection rate reported so far for this disease (93%) and bringing the number of known disease-causing mutations from 35 to 51. This is the first report to describe clustering of pathogenic mutations. Thirteen novel polymorphic alterations were characterized, confirming previous reports that TCOF1 has an unusually high rate of single-nucleotide polymorphisms (SNPs) within its coding region. We suggest a possible different mechanism leading to TCS or genetic heterogeneity for this condition, as we identified two families with no apparent pathogenic mutation in the gene. Furthermore, our data confirm the absence of genotype-phenotype correlation and reinforce that the apparent anticipation often observed in TCS families is due to ascertainment bias.
Assuntos
Disostose Mandibulofacial/genética , Proteínas Nucleares/genética , Fosfoproteínas/genética , Mutação Puntual , Análise Mutacional de DNA , Feminino , Marcadores Genéticos/genética , Humanos , Recém-Nascido , Masculino , Disostose Mandibulofacial/etiologia , Família Multigênica , Polimorfismo de Nucleotídeo Único/genética , Polimorfismo Conformacional de Fita Simples , Razão de Masculinidade , SíndromeRESUMO
The dimeric beta-barrel is a characteristic topology initially found in the transcriptional regulatory domain of the E2 DNA binding domain from papillomaviruses. We have previously described the kinetic folding mechanism of the human HPV-16 domain, and, as part of these studies, we present a structural characterization of the urea-denatured state of the protein. We have obtained a set of chemical shift assignments for the C-terminal domain in urea using heteronuclear NMR methods and found regions with persistent residual structure. Based on chemical shift deviations from random coil values, 3'J(NHN alpha) coupling constants, heteronuclear single quantum coherence peak intensities, and nuclear Overhauser effect data, we have determined clusters of residual structure in regions corresponding to the DNA binding helix and the second beta-strand in the folded conformation. Most of the structures found are of nonnative nature, including turn-like conformations. Urea denaturation at equilibrium displayed a loss in protein concentration dependence, in absolute parallel to a similar deviation observed in the folding rate constant from kinetic experiments. These results strongly suggest an alternative folding pathway in which a dimeric intermediate is formed and the rate-limiting step becomes first order at high protein concentrations. The structural elements found in the denatured state would collide to yield productive interactions, establishing an intermolecular folding nucleus at high protein concentrations. We discuss our results in terms of the folding mechanism of this particular topology in an attempt to contribute to a better understanding of the folding of dimers in general and intertwined dimeric proteins such as transcription factors in particular.
Assuntos
Proteínas de Ligação a DNA , Proteínas Oncogênicas Virais/química , Papillomaviridae/química , Ureia/química , Sequência de Aminoácidos , Sítios de Ligação , Dimerização , Humanos , Cinética , Espectroscopia de Ressonância Magnética , Dados de Sequência Molecular , Desnaturação Proteica , Dobramento de ProteínaRESUMO
We report on a four-generation inbred family including 10 individuals affected with a form of craniotubular dysplasia (CTD). All affected patients were born to consanguineous healthy parents; this finding, together with the equal sex ratio among affected individuals and the occurrence of only normal individuals among their offspring, indicates that the disease in this family is an autosomal recessive (AR) trait. Taking into account the segregation pattern of the disease in the family and the radiological characteristics of two young CTD patients, the most likely diagnosis for the defect is AR craniometaphyseal dysplasia (CMD). CMD is a CTD, with both autosomal dominant (AD) and recessive forms. The description of the present genealogy confirms the AR pattern of inheritance of some cases of CMD and contributes to a better delineation of the clinical spectrum of AR CMD, suggesting a more pronounced diaphyseal involvement in the AR compared with the AD CMD. Through genomewide scanning, we mapped the AR CMD to a 7 cM interval, between D6S302 and D6S1639, at 6q21-22 region. We have also excluded the positional candidate COL10A1 gene as being the responsible for this disorder. Curiously, a form of AR spondylocostal dysplasia (SD) also segregates in the family, including one affected individual with both conditions. The gene DLL3, mapped to 19q13 region, was recently found to be responsible for one form of AR SD; however, we did not find evidence of linkage between this 19q region and the SD segregating in our family, thus implying in genetic heterogeneity for AR SD.
Assuntos
Osso e Ossos/anormalidades , Cromossomos Humanos Par 6/genética , Colágeno Tipo I , Colágeno/genética , Anormalidades Craniofaciais/genética , Genes Recessivos , Osteocondrodisplasias/genética , Adulto , Idoso , Osso e Ossos/diagnóstico por imagem , Pré-Escolar , Mapeamento Cromossômico , Cromossomos Humanos Par 19/genética , Cadeia alfa 1 do Colágeno Tipo I , Anormalidades Craniofaciais/diagnóstico por imagem , DNA/análise , Feminino , Heterogeneidade Genética , Ligação Genética , Humanos , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Osteocondrodisplasias/diagnóstico por imagem , Linhagem , Fenótipo , RadiografiaRESUMO
During the last few years, it has been demonstrated that some syndromic craniosynostosis and short-limb dwarfism syndromes, a heterogeneous group comprising of 11 distinct clinical entities, are caused by mutations in one of three fibroblast growth factor receptor genes (FGFR1, FGFR2, and FGFR3). The present review list all mutations described to date in these three genes and the phenotypes associated with them. In addition, the tentative phenotype-genotype correlation is discussed, including the most suggested causative mechanisms for these conditions.
Assuntos
Mutação/genética , Proteínas Tirosina Quinases , Receptores Proteína Tirosina Quinases/genética , Receptores de Fatores de Crescimento de Fibroblastos/genética , Doenças do Desenvolvimento Ósseo/genética , Genótipo , Humanos , Malformações do Sistema Nervoso/genética , Fenótipo , Mutação Puntual , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos , Receptor Tipo 3 de Fator de Crescimento de FibroblastosRESUMO
Dominant mutations in three fibroblast growth factor receptor genes (FGFRs1-3) cause Crouzon, Jackson-Weiss, Pfeiffer, and Apert syndromes. In the present study, 50 Brazilian patients with these four syndromes (27 Apert, 17 Crouzon, 5 Pfeiffer, and 1 Jackson-Weiss patients) were screened for mutations in the FGFR1-3 genes. Except for one, all the Apert patients had either S252W (n = 16) or P253R (n = 10) mutations. The remaining Apert case is atypical with a mutation altering the splice site of FGFR2 exon IIIc. The Pfeiffer patients had mutations in one of the FGFR genes: three in FGFR2, one in FGFR1, and one in FGFR3. In contrast, only 8 of the 17 Crouzon patients studied had a mutation in either FGFR2 (n = 7) or FGFR3 locus (n = 1). Mutations in the FGFR2 locus account for most (93%) of our syndromic craniosynostotic cases, whereas 5% had mutations in the FGFR3 locus and only 2% had mutations in the FGFR1 gene. Except for one, all the other mutations were reported previously in craniosynostotic patients from other populations. Interestingly, the mutation C278F, previously described in Crouzon and Pfeiffer cases, was here identified in a familial case with Jackson-Weiss. Also, unexpectedly, a common mutation altering the splice site of the FGFR2 exon IIIc was found in one Apert and two Pfeiffer patients. In addition, we identified a new mutation (A337P) in the FGFR2 exon IIIc associated with Crouzon phenotype.