title: Maternal mutations of FOXF1 cause alveolar capillary dysplasia despite not being imprinted.
abstract: 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.
authors.affiliation: Department of Neonatology, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Alsina Casanova
authors.affiliation: Imprinting and Cancer Group, Cancer Epigenetic and Biology Program, Bellvitge Biomedical Research Institute, Hospital Duran & Reynals, Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Monteagudo-Sánchez
authors.affiliation: Department of Neonatology, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.
authors.forename: Luciana
authors.initials: L
authors.lastname: Rodiguez Guerineau
authors.affiliation: Genetics, Reproduction and Development laboratories (GreD), CNRS, UMR6247, Clermont Université, INSERM U931, Clermont-Ferrand, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Court
authors.affiliation: Department of Neonatology, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Gazquez Serrano
authors.affiliation: Laboratory of Molecular Genètics, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.
authors.forename: Loreto
authors.initials: L
authors.lastname: Martorell
authors.affiliation: Department of Pathology, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.
authors.forename: Carlota
authors.initials: C
authors.lastname: Rovira Zurriaga
authors.affiliation: Genetics and Genomic Medicine Programme, Institute of Child Health, University College London, London, UK.
authors.forename: Gudrun E
authors.initials: GE
authors.lastname: Moore
authors.affiliation: Genetics and Genomic Medicine Programme, Institute of Child Health, University College London, London, UK.
authors.forename: Miho
authors.initials: M
authors.lastname: Ishida
authors.affiliation: Department of Surgery, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Castañon
authors.affiliation: Section of Neonatology, Department of Pediatrics, Hospital Sant Pau, Barcelona, Spain.
authors.forename: Elisenda
authors.initials: E
authors.lastname: Moliner Calderon
authors.affiliation: Imprinting and Cancer Group, Cancer Epigenetic and Biology Program, Bellvitge Biomedical Research Institute, Hospital Duran & Reynals, Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Monk
authors.affiliation: Department of Neonatology, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Moreno Hernando
mesh_terms: D055028:Comparative Genomic Hybridization; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D018392:Genomic Imprinting; D006801:Humans; D006976:Hypertension, Pulmonary; D007231:Infant, Newborn; D000072741:Maternal Inheritance / Q000235:genetics; D009154:Mutation; D010547:Persistent Fetal Circulation Syndrome / Q000150:complications / Q000235:genetics* / Q000473:pathology; D011247:Pregnancy; D011650:Pulmonary Alveoli / Q000002:abnormalities* / Q000473:pathology; D014430:Twins, Monozygotic
chemical_list: C098521:FOXF1 protein, human; D051858:Forkhead Transcription Factors
keywords: FOXF1; alveolar capillary dysplasia; imprinting; methylation