RESUMEN
Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare cause of pulmonary hypertension in newborns. Maternally inherited point mutations in Forkhead Box F1 gene (FOXF1), deletions of the gene, or its long-range enhancers on the maternal allele are responsible for this neonatal lethal disorder. Here, we describe monozygotic twins and one full-term newborn with ACD and gastrointestinal malformations caused by de novo mutations of FOXF1 on the maternal-inherited alleles. Since this parental transmission is consistent with genomic imprinting, the parent-of-origin specific monoallelic expression of genes, we have undertaken a detailed analysis of both allelic expression and DNA methylation. FOXF1 and its neighboring gene FENDRR were both biallelically expressed in a wide range of fetal tissues, including lung and intestine. Furthermore, detailed methylation screening within the 16q24.1 regions failed to identify regions of allelic methylation, suggesting that disrupted imprinting is not responsible for ACDMPV.
Asunto(s)
Factores de Transcripción Forkhead/genética , Impresión Genómica , Síndrome de Circulación Fetal Persistente/genética , Alveolos Pulmonares/anomalías , Hibridación Genómica Comparativa , Metilación de ADN/genética , Femenino , Humanos , Hipertensión Pulmonar , Recién Nacido , Herencia Materna/genética , Mutación , Síndrome de Circulación Fetal Persistente/complicaciones , Síndrome de Circulación Fetal Persistente/patología , Embarazo , Alveolos Pulmonares/patología , Gemelos MonocigóticosRESUMEN
BACKGROUND: Postnatal growth restriction remains one of the most common problems of very preterm infants (VPI). Chorioamnionitis is a frequent cause of prematurity. Both have been related to worse postnatal outcomes. OBJECTIVES: To evaluate the influence of histological chorioamnionitis (CA) on postnatal growth in very premature infants. METHODS: Retrospective one-to-one matched cohort study assessing growth in infants born at or below 32.0 weeks gestation from mothers for whom histological examination of the placenta was available. Newborns with histological CA were matched and compared with those without it. Postnatal growth was recorded at admission, 14 days of life, 28 days of life and 36 weeks postmenstrual age (PMA). Nutritional support and clinical outcomes were used as covariables. RESULTS: Eighty-eight patients were included: 44 with fetal or/and maternal placental inflammation, and 44 without histological CA (41% with vasculopathy findings and 59% without). Baseline characteristics were similar between the groups. Change in weight z-scores at 14 days of life, 28 days of life, 36 weeks PMA or at discharge were similar in both groups, with a steady fall and no signs of catch-up. No differences were found in enteral and parenteral nutritional intakes between groups. CONCLUSIONS: Histological CA did not affect postnatal growth of very preterm infants after matching for birth weight z-scores with non-CA newborns.