RESUMEN
Pathogenic heterozygous variants in the NOTCH1 gene are known to be associated with both left and right-sided congenital cardiac anomalies with strikingly incomplete penetrance and variable phenotypic expressivity. De novo NOTCH1 whole gene deletion has been reported rarely in the literature and its association with cardiac defects is less well established. Here, we report four cases of NOTCH1 gene deletion from two families associated with a spectrum of congenital heart defects from bicuspid aortic valve to complex cardiac anomalies. This is the first description of a familial NOTCH1 deletion, showing apparently high penetrance, which may be unique to this mechanism of disease. Immunohistochemical staining of cardiac tissue demonstrated reduced levels of NOTCH1 expression in both the left and right ventricular outflow tracts. These cases suggest that haploinsufficiency caused by NOTCH1 gene deletion is associated with both mild and severe cardiac defects, similar to those caused by pathogenic variants in the gene, but with apparently higher, if not complete, penetrance.
Asunto(s)
Cardiopatías Congénitas/genética , Enfermedades de las Válvulas Cardíacas/genética , Receptor Notch1/genética , Enfermedad de la Válvula Aórtica Bicúspide/genética , Preescolar , Femenino , Eliminación de Gen , Haploinsuficiencia/genética , Heterocigoto , Humanos , Masculino , Linaje , Penetrancia , EmbarazoRESUMEN
OBJECTIVE: Folate deficiency in early pregnancy and maternal adiposity, independent of folate intake, lead to a greater risk of neural tube defects in infants. Atypical antipsychotics cause various degrees of weight gain. The authors assessed folate status and obesity among patients with schizophrenia receiving atypical antipsychotics. METHOD: A sample of 70 inpatients and outpatients (21 of them women) who were taking antipsychotics was randomly selected. Body weight, body mass index, daily folate intake, and folate serum concentrations were determined. RESULTS: The majority of the patients were overweight. Only eight of 37 patients had folate intake above 400 microg/day, the level shown to be protective against neural tube defects. Mean serum folate was significantly lower than in a general hospital group of 810 patients. CONCLUSIONS: Women with schizophrenia who take atypical antipsychotics have a higher risk of neural tube defects in their infants because of the associated low intake of folate and obesity.