RESUMO
BACKGROUND: Phelan-McDermid syndrome is characterized by a range of neurodevelopmental phenotypes with incomplete penetrance and variable expressivity. It is caused by a variable size and breakpoint microdeletions in the distal long arm of chromosome 22, referred to as 22q13.3 deletion syndrome, including the SHANK3 gene. Genetic defects in a growing number of neurodevelopmental genes have been shown to cause genome-wide disruptions in epigenomic profiles referred to as epi-signatures in affected individuals. RESULTS: In this study we assessed genome-wide DNA methylation profiles in a cohort of 22 individuals with Phelan-McDermid syndrome, including 11 individuals with large (2 to 5.8 Mb) 22q13.3 deletions, 10 with small deletions (< 1 Mb) or intragenic variants in SHANK3 and one mosaic case. We describe a novel genome-wide DNA methylation epi-signature in a subset of individuals with Phelan-McDermid syndrome. CONCLUSION: We identified the critical region including the BRD1 gene as responsible for the Phelan-McDermid syndrome epi-signature. Metabolomic profiles of individuals with the DNA methylation epi-signature showed significantly different metabolomic profiles indicating evidence of two molecularly and phenotypically distinct clinical subtypes of Phelan-McDermid syndrome.
Assuntos
Deleção Cromossômica , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 22/genética , Metilação de DNA/genética , Variação Genética , Genótipo , Fenótipo , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Estudo de Associação Genômica Ampla , Humanos , MasculinoAssuntos
Síndrome CHARGE/genética , Síndrome CHARGE/patologia , DNA Helicases/genética , Proteínas de Ligação a DNA/genética , Fenótipo , Síndrome CHARGE/diagnóstico , Códon sem Sentido/genética , Hibridização Genômica Comparativa , Análise Mutacional de DNA , Feminino , Humanos , Íntrons/genética , Masculino , Mutação de Sentido Incorreto/genética , Sítios de Splice de RNA/genéticaRESUMO
Activated C protein resistance is a common coagulation defect caused by factor V Leiden mutation and is associated with an augmented risk of predominantly venous thrombosis. Augmented tendency to arterial thrombosis is sporadically reported. This case report describes femoropopliteal thrombosis in a young patient with heterozygous V Leiden factor mutation. Progressive thrombotic occlusion required amputation of the forefoot which resulted in stump dehiscence. Poor blood supply to the perilesional substrate delayed wound healing. An optimal though not yet definitive result was achieved after months of accurate medication. The criticality of lower limb ischemia in an otherwise healthy young patient underscores the grave impact this condition can have on the patient's quality of life and on health care costs.
Assuntos
Fator V/genética , Artéria Femoral , Mutação , Artéria Poplítea , Trombose/genética , Resistência à Proteína C Ativada/genética , Adulto , Amputação Cirúrgica/efeitos adversos , Amputação Cirúrgica/métodos , Heterozigoto , Humanos , Masculino , Trombose/complicações , Trombose/cirurgia , CicatrizaçãoRESUMO
Sensorineural hearing loss (SNHL) is a common defect with a multifactorial etiology. Congenital cytomegalovirus infection (cCMV) is the most common infectious cause, and its early detection allows a prompt pharmacological treatment that can improve hearing prognosis. In a consistent percentage of profound SNHL, genetic causes and/or inner ear malformations are involved; their prompt diagnosis might change therapeutic options. This study reports a case of a 3- year-old female patient with symptomatic cCMV infection who also exhibits developmental delay, dysmorphic facial features, bilateral hearing loss, and cochlear incomplete partition, type 2, in 7q21.3 deletion. This deletion includes the genes DLX5 and DLX6 , which could be the candidate genes for the ear malformation named incomplete partition, type 2.
Assuntos
Cistos Aracnóideos/complicações , Cistos/complicações , Cardiopatias/complicações , Doenças Renais Císticas/complicações , Cistos Aracnóideos/diagnóstico , Cistos/diagnóstico , Cardiopatias/diagnóstico , Humanos , Doenças Renais Císticas/diagnóstico , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
Recently, many experiments have highlighted the advantage of using polycapillary optics for x-ray fluorescence studies. We have developed a special confocal scheme for micro x-ray fluorescence measurements that enables us to obtain not only elemental mapping of the sample but also simultaneously its own x-ray imaging. We have designed the prototype of a compact x-ray spectrometer characterized by a spatial resolution of less than 100 microm for fluorescence and less than 10 microm for imaging. A couple of polycapillary lenses in a confocal configuration together with a silicon drift detector allow elemental studies of extended samples (approximately 3 mm) to be performed, while a CCD camera makes it possible to record an image of the same samples with 6 microm spatial resolution, which is limited only by the pixel size of the camera. By inserting a compound refractive lens between the sample and the CCD camera, we hope to develop an x-ray microscope for more enlarged images of the samples under test.
RESUMO
Papillary fibroelastomas are very rare cardiac tumours that can present with embolization of coronary and peripheral arteries and sudden death. The diagnosis can be made by two-dimensional or transoesophageal echocardiography. A 53-year-old man with an aortic valve papillary fibroelastoma who presented with several transient ischaemic attacks is reported.