title: A 16q deletion involving FOXF1 enhancer is associated to pulmonary capillary hemangiomatosis.
abstract: BACKGROUND
  Pulmonary capillary hemangiomatosis (PCH) is an uncommon pulmonary disorder, with variable clinical features depending on which lung structure is affected, and it is usually linked to pulmonary arterial hypertension. Congenital PCH has been very rarely described and, so far, the only causative gene identified is EIF2AK4, which encodes for a translation initiation factor. However, not all PCH cases might carry a mutation in this gene.
  
  
  METHODS
  We report the clinical and cytogenetic characterization of a patient (male, newborn, first child of healthy non-consanguineous parents) died after three days of life with severe neonatal pulmonary hypertension, due to diffuse capillary hemangiomatosis diagnosed post mortem. Conventional karyotyping, Microarray-Based Comparative Genomic Hydridization (CGHa) and quantitative PCR were performed. CGHa revealed a heterozygous chromosome 16q23.3q24.1 interstitial deletion, spanning about 2.6 Mb and involving a FOXF1 gene enhancer. Quantitative PCR showed that the proband's deletion was de novo. Microsatellite analysis demonstrate that the deletion occurred in the maternal chromosome 16.
  
  
  CONCLUSIONS
  FOXF1 loss of function mutation have been so far identified in alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV), a lung disease different from PCH. Our data suggest the hypothesis that disruption of the FOXF1 gene enhancer could be a genetic determinant of PCH. Moreover, our findings support the idea that FOXF1 is a paternally imprinted gene.
authors.affiliation: Dipartimento di Medicina di Laboratorio, Azienda Ospedaliero-Universitaria S. Maria della Misericordia, Udine, Italy. dellorusso.patrizia@aoud.sanita.fvg.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Dello Russo
authors.affiliation: Dipartimento di Medicina di Laboratorio, Azienda Ospedaliero-Universitaria S. Maria della Misericordia, Udine, Italy. franzoni.alessandra@aoud.sanita.fvg.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Franzoni
authors.affiliation: Dipartimento di Scienze Mediche e Biologiche, Università di Udine, Piazzale Kolbe 4, 33100, Udine, Italy. baldan.federica@spes.uniud.it.
authors.forename: Federica
authors.initials: F
authors.lastname: Baldan
authors.affiliation: Dipartimento di Scienze Mediche e Biologiche, Università di Udine, Piazzale Kolbe 4, 33100, Udine, Italy. cinzia.puppin@uniud.it.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Puppin
authors.affiliation: Dipartimento di Medicina di Laboratorio, Azienda Ospedaliero-Universitaria S. Maria della Misericordia, Udine, Italy. demaglio.giovanna@aoud.sanita.fvg.
authors.forename: Giovanna
authors.initials: G
authors.lastname: De Maglio
authors.affiliation: Dipartimento Materno-infantile, Azienda Ospedaliero-Universitaria S. Maria della Misericordia, Udine, Italy. pittini.carla@aoud.sanita.fvg.it.
authors.forename: Carla
authors.initials: C
authors.lastname: Pittini
authors.affiliation: Dipartimento Materno-infantile, Azienda Ospedaliero-Universitaria S. Maria della Misericordia, Udine, Italy. cattarossi.luigi@aoud.sanita.fvg.it.
authors.forename: Luigi
authors.initials: L
authors.lastname: Cattarossi
authors.affiliation: Dipartimento di Medicina di Laboratorio, Azienda Ospedaliero-Universitaria S. Maria della Misericordia, Udine, Italy. pizzolitto.stefano@aoud.sanita.fvg.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Pizzolitto
authors.affiliation: Dipartimento di Medicina di Laboratorio, Azienda Ospedaliero-Universitaria S. Maria della Misericordia, Udine, Italy. giuseppe.damante@uniud.it.|Dipartimento di Scienze Mediche e Biologiche, Università di Udine, Piazzale Kolbe 4, 33100, Udine, Italy. giuseppe.damante@uniud.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Damante
mesh_terms: D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D055028:Comparative Genomic Hybridization / Q000379:methods; D004742:Enhancer Elements, Genetic; D051858:Forkhead Transcription Factors / Q000235:genetics*; D017353:Gene Deletion; D018392:Genomic Imprinting; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D007231:Infant, Newborn; D008297:Male
chemical_list: C098521:FOXF1 protein, human; D051858:Forkhead Transcription Factors