RESUMO
Phospholipase Cepsilon is a novel class of phosphoinositide-specific phospholipase C, identified as a downstream effector of Ras and Rap small GTPases. We report here the first genetic analysis of its physiological function with mice whose phospholipase Cepsilon is catalytically inactivated by gene targeting. The hearts of mice homozygous for the targeted allele develop congenital malformations of both the aortic and pulmonary valves, which cause a moderate to severe degree of regurgitation with mild stenosis and result in ventricular dilation. The malformation involves marked thickening of the valve leaflets, which seems to be caused by a defect in valve remodeling at the late stages of semilunar valvulogenesis. This phenotype has a remarkable resemblance to that of mice carrying an attenuated epidermal growth factor receptor or deficient in heparin-binding epidermal growth factor-like growth factor. Smad1/5/8, which is implicated in proliferation of the valve cells downstream of bone morphogenetic protein, shows aberrant activation at the margin of the developing semilunar valve tissues in embryos deficient in phospholipase Cepsilon. These results suggest a crucial role of phospholipase Cepsilon downstream of the epidermal growth factor receptor in controlling semilunar valvulogenesis through inhibition of bone morphogenetic protein signaling.
Assuntos
Valva Aórtica/anormalidades , Valva Aórtica/embriologia , Valva Pulmonar/anormalidades , Valva Pulmonar/embriologia , Fosfolipases Tipo C/fisiologia , Alelos , Animais , Valva Aórtica/imunologia , Defeito do Septo Aortopulmonar/genética , Proteínas Morfogenéticas Ósseas/fisiologia , Cardiomiopatia Dilatada/etiologia , Proteínas de Ligação a DNA/análise , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Receptores ErbB/deficiência , Receptores ErbB/genética , Receptores ErbB/fisiologia , Marcação de Genes , Doenças das Valvas Cardíacas/complicações , Doenças das Valvas Cardíacas/genética , Ventrículos do Coração/patologia , Camundongos , Camundongos Mutantes , Mutação/genética , Fosfoinositídeo Fosfolipase C , Fosfoproteínas/análise , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Valva Pulmonar/imunologia , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Proteínas Smad , Proteína Smad1 , Proteína Smad5 , Proteína Smad8 , Transativadores/análise , Transativadores/genética , Transativadores/metabolismo , Fosfolipases Tipo C/análise , Fosfolipases Tipo C/genéticaRESUMO
Aortopulmonary window (APW) is a rare malformation. We recently operated on a child with APW, ventricular septal defect, right aortic arch, and anomalous right coronary artery from the APW. This patient also had a chromosomal abnormality. He underwent the repair of this complex lesion in a staged operation.
Assuntos
Defeito do Septo Aortopulmonar/cirurgia , Anomalias dos Vasos Coronários/cirurgia , Defeito do Septo Aortopulmonar/diagnóstico , Defeito do Septo Aortopulmonar/genética , Cromossomos Humanos Par 3 , Cromossomos Humanos Par 7 , Anomalias dos Vasos Coronários/diagnóstico , Anomalias dos Vasos Coronários/genética , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/cirurgia , Hemodinâmica/fisiologia , Humanos , Lactente , Masculino , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/cirurgia , Reoperação , Translocação Genética/genéticaRESUMO
Anomalous left pulmonary artery (vascular sling) is a congenital anomaly in which the vascular structure arises either from the posterior surface of the right pulmonary artery, or from the main pulmonary artery and courses to the left lung between the posterior surface of the trachea and the anterior surface of the esophagus. It may cause compression on the tracheobronchial tree. It is a rare condition leading to death in the first months of life, if it is not corrected. Its diagnosis is quite difficult because it usually presents non specific symptoms frequently associated to diffuse tracheal stenosis. The authors present a clinical case of a newborn with trisomy 21 who had a left pulmonary artery sling associated to tracheal stenosis and congenital heart disease (complete atrioventricular septal defect). They review the literature, particular in what concerns embryopathogenesis, the difficulties in establishing the diagnosis and the surgery which must be performed as soon as possible.
Assuntos
Defeito do Septo Aortopulmonar/genética , Artéria Pulmonar/anormalidades , Defeito do Septo Aortopulmonar/complicações , Síndrome de Down , Feminino , Humanos , Recém-Nascido , Estenose Traqueal/complicaçõesRESUMO
We describe a 37-week gestation female infant who was born with a terminal 2q deletion. Both of her parents had normal chromosomes. This infant had multiple anomalies, including hypertelorism, short palpebral fissures, microphthalmia, cleft lip/cleft palate, and abnormal ears. Autopsy documented Dandy-Walker malformation with severe hydrocephalus, aortopulmonary window, secundum atrial septal defect, duodenal atresia, incomplete rotation of the bowel, gonadal dysgenesis, uterus didelphys, and musculoskeletal defects. Compared with the other 6 children with 2q terminal deletion documented in the literature, this patient is the most severely affected. This patient is also the only one documented to have died and undergone autopsy examination. The findings in this case provide more data for the eventual description of a "terminal 2q deletion syndrome" and suggest that some abnormalities, such as gonadal dysgenesis, may be present in living children with this chromosome abnormality.