Assuntos
Carcinoma Papilar/patologia , Proteína SMARCB1/genética , Neoplasias da Medula Espinal/patologia , Carcinoma Papilar/genética , Carcinoma Papilar/cirurgia , Humanos , Laminectomia , Masculino , Pessoa de Meia-Idade , Neoplasias da Medula Espinal/genética , Neoplasias da Medula Espinal/cirurgia , Vértebras Torácicas , Resultado do TratamentoRESUMO
Periodic fever, aphthous stomatitis, pharyngitis and adenopathy (PFAPA) syndrome is an auto-inflammatory disease for which a genetic basis has been postulated. Nevertheless, in contrast to the other periodic fever syndromes, no candidate genes have yet been identified. By cloning, following long insert size paired-end sequencing, of a de novo chromosomal translocation t(10;17)(q11.2;p13) in a patient with typical PFAPA syndrome lacking mutations in genes associated with other periodic fever syndromes we identified SPAG7 as a candidate gene for PFAPA. SPAG7 protein is expressed in tissues affected by PFAPA and has been functionally linked to antiviral and inflammatory responses. Haploinsufficiency of SPAG7 due to a microdeletion at the translocation breakpoint leading to loss of exons 2-7 from one allele was associated with PFAPA in the index. Sequence analyses of SPAG7 in additional patients with PFAPA point to genetic heterogeneity or alternative mechanisms of SPAG7 deregulation, such as somatic or epigenetic changes.
Assuntos
Antígenos de Superfície/genética , Febre/genética , Estudos de Associação Genética , Doenças Linfáticas/genética , Faringite/genética , Estomatite Aftosa/genética , Criança , Pré-Escolar , Pontos de Quebra do Cromossomo , Feminino , Haploinsuficiência , Humanos , Lactente , Cariotipagem , Masculino , Síndrome , Translocação GenéticaRESUMO
This article presents the first physical mapping carried out in the Senegalese sole (Solea senegalensis), an important marine fish species of Southern Europe. Eight probes were designated to pick up genes of interest in aquaculture (candidate genes) from a bacterial artificial chromosome (BAC) library using a method of rapid screening based on a 4-dimension PCR. Seven known and 3 unknown clones were isolated and labeled. The 10 BAC clones were used as probes to map the karyotype of the species by fluorescence in situ hybridization (FISH). Nine out of the 10 clones were localized in only 1 chromosome pair, whereas the remaining one hybridized on 2 chromosome pairs. The 2-color FISH experiments showed colocation of 4 probes in 2 chromosome pairs. In addition, 2-color FISH was carried out both with 5S rDNA and the BAC containing the lysozyme gene published previously. This first genetic map of the Senegalese sole represents a starting point for future studies of the sole genome. In addition, 7 out of the 10 BAC clones were sequenced using next-generation sequencing, and bioinformatic characterization of the sequences was carried out. Hence the anchoring of the sequences to specific chromosomes or chromosome arms is now possible, leading to an initial scaffold of the Senegalese sole genome.
Assuntos
Linguados/genética , Animais , Cromossomos Artificiais Bacterianos/genética , Loci Gênicos , Hibridização in Situ Fluorescente , Mapeamento Físico do Cromossomo , RNA não Traduzido/genéticaRESUMO
Male external genital differentiation is accompanied by implementation of a long-term, male-specific gene expression pattern indicating androgen programming in cultured genital fibroblasts. We hypothesized the existence of an epigenetic background contributing to this phenomenon. DNA methylation levels in 2 normal scrotal fibroblast strains from 46,XY males compared to 2 labia majora fibroblast strains from 46,XY females with complete androgen insensitivity syndrome (AIS) due to androgen receptor (AR) mutations were analyzed by Illumina GoldenGate methylation arrays®. Results were validated with pyrosequencing in labia majora fibroblast strains from fifteen 46,XY patients and compared to nine normal male scrotal fibroblast strains. HOXA5 showed a significantly higher methylation level in complete AIS. This finding was confirmed by bisulfite pyrosequencing of 14 CpG positions within the HOXA5 promoter in the same strains. Extension of the 2 groups revealed a constant low HOXA5 methylation pattern in the controls in contrast to a highly variable methylation pattern in the AIS patients. HOXA5 represents a candidate gene of androgen-mediated promoter methylation. The constantly low HOXA5 DNA methylation level of normal male scrotal fibroblast strains and the frequently high methylation levels in labia majora fibroblast strains in AIS indicate for the first time that androgen programming in sexual differentiation is not restricted to global gene transcription but also occurs at the epigenetic level.
Assuntos
Epigênese Genética/genética , Proteínas de Homeodomínio/genética , Receptores Androgênicos/genética , Metilação de DNA/genética , Feminino , Humanos , Masculino , Mutação , Regiões Promotoras Genéticas/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The authors report the case of unusual auscultatory findings, multiple systolic clicks, in a patient with a Starr-Edwards model 1 260 aortic valve replacement, six years after the implantation. The aetiology of this anomaly appears to be incorrect positioning of the prosthetic valve ring.
