RESUMO
Interstitial microduplication of 3q29 has been recently described. Individuals with this syndrome have widely variable phenotypes. We describe the first clinical case with a 1.607 Mb duplication at 3q29 (chr3: 195,731,956-197,339,329), accompanied by severe intellectual disability, epilepsy, and cerebral palsy. This duplication involves 22 genes; PAK2, DLG1, BDH1, and FBXO45 are implicated in neuronal development and synaptic function and could play an important role in this syndrome. We propose considering genetic studies, particularly array comparative genomic hybridization, in patients with epilepsy and/or cerebral palsy of unknown etiology when dysmorphic features are present.
Assuntos
Paralisia Cerebral/genética , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Duplicação Cromossômica/genética , Epilepsia/genética , Deficiência Intelectual/genética , Fenótipo , Encéfalo/patologia , Paralisia Cerebral/diagnóstico , Criança , Hibridização Genômica Comparativa , Epilepsia/diagnóstico , Feminino , Humanos , Deficiência Intelectual/diagnóstico , Imageamento por Ressonância MagnéticaRESUMO
LBX1 plays a cardinal role in neuronal and muscular development in animal models. Its function in humans is unknown; it has been reported as a candidate gene for idiopathic scoliosis. Our goal is to document the first clinical case of a microduplication at 10q24.31 (chr10:102927883-103053612, hg19), affecting exclusively LBX1. The patient, a 12-year-old girl, showed attention problems, dyspraxia, idiopathic congenital scoliosis, and marked hypotrophy of paravertebral muscles. Her paternal aunt had a severe and progressive myopathy with a genetic study that revealed the same duplication. We propose to consider genetic studies, particularly of LBX1, in patients with scoliosis and/or hypotrophy-hypoplasia of paravertebral muscles of unknown etiology.
Assuntos
Duplicação Cromossômica , Cromossomos Humanos Par 10 , Doenças Musculares/genética , Escoliose/genética , Criança , Hibridização Genômica Comparativa , Feminino , Estudos de Associação Genética , Proteínas de Homeodomínio/genética , Humanos , Imageamento por Ressonância Magnética , Doenças Musculares/diagnóstico , Fenótipo , Radiografia , Escoliose/diagnóstico , Espanha , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/patologia , Fatores de Transcrição/genéticaRESUMO
Fever of unknown origin is a diagnostic challenge. Among its causes are of large caliber vessels vasculitis (LCVV), including Takayasu arteritis (TA) and giant cell arteritis (GCA). Early diagnosis is vital to prevent fibrosis of the vessel wall, and consequently, stenoses, aneurysms or occlusions. Imaging techniques can be of great help in recent years, highlighting the temporal artery through ultrasound, MRI and PET-CT.
Assuntos
Arterite de Células Gigantes/diagnóstico , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Arterite de Takayasu/diagnóstico , Tomografia Computadorizada por Raios X , Adulto , Idoso , Feminino , Arterite de Células Gigantes/diagnóstico por imagem , Humanos , Arterite de Takayasu/diagnóstico por imagemRESUMO
CD69 is the earliest activation antigen expressed on T lymphocytes upon stimulation through the TCR, or with stimuli that mimic TCR triggering. Here we describe that the phorbol ester PMA and a calcium ionophore had a synergistic effect on both CD69 antigen expression and promoter activity in Jurkat cells, that was sensitive to cyclosporin A (CsA). CD69 promoter analysis indicated that the sequence -78 to +16 contained the elements responsible for PMA and PMA plus calcium ionophore induction, as well as CsA inhibition. Mutagenesis of two previously described AP-1 motifs did not affect either the basal or the inducible promoter activities. Electrophoretic mobility shift assays allowed the identification of three novel inducible complexes composed by Egr-1/Egr-3, Egr-1, and ATF-3/Fos. Mutation of each sequence resulted in a partial reduction of the basal promoter activity, whereas the inducibility by PMA plus calcium ionophore remained almost unaffected. It was necessary to combine at least two mutations to obtain a significative or complete reduction of the response to the mitogenic stimulus. These results indicate that the inducible expression of CD69 gene by mitogenic signals is regulated by multiple cis-acting elements and by the interplay of transcription factors of the AP-1, EGR and ATF/CREB families.