title: Pathogenesis of congenital diaphragmatic hernia: additional clues regarding the involvement of the endothelin system.
abstract: Congenital diaphragmatic hernia (CDH) has an incidence of around 1/3,000 births. The pathogenesis of this developmental anomaly remains largely unknown and the description of small chromosomal imbalances in cases of CDH is of major interest for the identification of candidate genes. We report on a tandem 4q31.23 triplication encompassing the EDNRA gene identified by array-CGH in a male presenting an isolated left postero-lateral CDH. This copy number variation was inherited from the asymptomatic father, carrier of a size-identical duplication. We demonstrate that EDNRA mRNA is over-expressed in the proband in blood tissue. Consistent with the expression of EDNRA in the developing diaphragm and the observation that the endothelin system is up-regulated in human and animal models of CDH, we conclude that the EDNRA triplication may be the cause of CDH in our patient.
authors.affiliation: Université Lille Nord de France, CHRU Lille, France; Service de Gynécologie-Obstétrique, Hôpital Jeanne de Flandre, CHRU Lille, France.
authors.forename: Violette
authors.initials: V
authors.lastname: Mesdag
authors.forename: Joris
authors.initials: J
authors.lastname: Andrieux
authors.forename: Capucine
authors.initials: C
authors.lastname: Coulon
authors.forename: Thomas
authors.initials: T
authors.lastname: Pennaforte
authors.forename: Laurent
authors.initials: L
authors.lastname: Storme
authors.forename: Sylvie
authors.initials: S
authors.lastname: Manouvrier-Hanu
authors.forename: Florence
authors.initials: F
authors.lastname: Petit
mesh_terms: D002894:Chromosomes, Human, Pair 4; D055028:Comparative Genomic Hybridization; D065630:Hernias, Diaphragmatic, Congenital / Q000175:diagnosis / Q000209:etiology*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D010641:Phenotype; D044022:Receptor, Endothelin A / Q000235:genetics; D014314:Trisomy
chemical_list: D044022:Receptor, Endothelin A
keywords: 4q31.23 triplication; congenital diaphragmatic hernia; endothelin receptor A; endothelin-1, pulmonary hypertension