title: VEGF: a modifier of the del22q11 (DiGeorge) syndrome?
abstract: Hemizygous deletion of chromosome 22q11 (del22q11) causes thymic, parathyroid, craniofacial and life-threatening cardiovascular birth defects in 1 in 4,000 infants. The del22q11 syndrome is likely caused by haploinsufficiency of TBX1, but its variable expressivity indicates the involvement of additional modifiers. Here, we report that absence of the Vegf164 isoform caused birth defects in mice, reminiscent of those found in del22q11 patients. The close correlation of birth and vascular defects indicated that vascular dysgenesis may pathogenetically contribute to the birth defects. Vegf interacted with Tbx1, as Tbx1 expression was reduced in Vegf164-deficient embryos and knocked-down vegf levels enhanced the pharyngeal arch artery defects induced by tbx1 knockdown in zebrafish. Moreover, initial evidence suggested that a VEGF promoter haplotype was associated with an increased risk for cardiovascular birth defects in del22q11 individuals. These genetic data in mouse, fish and human indicate that VEGF is a modifier of cardiovascular birth defects in the del22q11 syndrome.
authors.affiliation: The Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Stalmans
authors.forename: Diether
authors.initials: D
authors.lastname: Lambrechts
authors.forename: Frederik
authors.initials: F
authors.lastname: De Smet
authors.forename: Sandra
authors.initials: S
authors.lastname: Jansen
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Sunit
authors.initials: S
authors.lastname: Maity
authors.forename: Paige
authors.initials: P
authors.lastname: Kneer
authors.forename: Maren
authors.initials: M
authors.lastname: von der Ohe
authors.forename: Ann
authors.initials: A
authors.lastname: Swillen
authors.forename: Christa
authors.initials: C
authors.lastname: Maes
authors.forename: Marc
authors.initials: M
authors.lastname: Gewillig
authors.forename: Daniel G M
authors.initials: DG
authors.lastname: Molin
authors.forename: Peter
authors.initials: P
authors.lastname: Hellings
authors.forename: Thurid
authors.initials: T
authors.lastname: Boetel
authors.forename: Maartin
authors.initials: M
authors.lastname: Haardt
authors.forename: Veerle
authors.initials: V
authors.lastname: Compernolle
authors.forename: Mieke
authors.initials: M
authors.lastname: Dewerchin
authors.forename: Stephane
authors.initials: S
authors.lastname: Plaisance
authors.forename: Robert
authors.initials: R
authors.lastname: Vlietinck
authors.forename: Beverly
authors.initials: B
authors.lastname: Emanuel
authors.forename: Adriana C
authors.initials: AC
authors.lastname: Gittenberger-de Groot
authors.forename: Peter
authors.initials: P
authors.lastname: Scambler
authors.forename: Bernice
authors.initials: B
authors.lastname: Morrow
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Driscol
authors.forename: Lieve
authors.initials: L
authors.lastname: Moons
authors.forename: Camila V
authors.initials: CV
authors.lastname: Esguerra
authors.forename: Geert
authors.initials: G
authors.lastname: Carmeliet
authors.forename: Annett
authors.initials: A
authors.lastname: Behn-Krappa
authors.forename: Koen
authors.initials: K
authors.lastname: Devriendt
authors.forename: Désiré
authors.initials: D
authors.lastname: Collen
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Conway
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000002:abnormalities; D002872:Chromosome Deletion; D000013:Congenital Abnormalities / Q000235:genetics; D004062:DiGeorge Syndrome / Q000235:genetics*; D016228:Endothelial Growth Factors / Q000235:genetics*; D005145:Face / Q000002:abnormalities; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008222:Lymphokines / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D039942:Neuropilin-1 / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics; D012886:Skull / Q000002:abnormalities; D020825:T-Box Domain Proteins / Q000235:genetics; D013950:Thymus Gland / Q000002:abnormalities; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D015027:Zebrafish
chemical_list: D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D020033:Protein Isoforms; D020825:T-Box Domain Proteins; C491573:Tbx1 protein, mouse; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D039942:Neuropilin-1