VEGF: A modifier of the de122q11 (DiGeorge) syndrome?

Ingeborg Stalmans, Diether Lambrechts, Frederik De Smet, Sandra Jansen, Jian Wang, Sunit Maity, Paige Kneer, Maren Von Der Ohe, Ann Swillen, Christa Maes, Marc Gewillig, Daniel G.M. Molin, Peter Hellings, Thurid Boetel, Maartin Haardt, Veerle Compernolle, Mieke Dewerchin, Stephane Plaisance, Robert Vlietinck, Beverly EmanuelAdriana C. Gittenberger-de Groot, Peter Scambler, Bernice Morrow, Deborah A. Driscol, Lieve Moons, Camila V. Esguerra, Geert Carmeliet, Annett Behn-Krappa, Koen Devriendt, Désiré Collen, Simon J. Conway, Peter Carmeliet

Research output: Contribution to journalArticlepeer-review

258 Scopus citations


Hemizygous deletion of chromosome 22q11 (de122q11) causes thymic, parathyroid, craniofacial and life-threatening cardiovascular birth defects in 1 in 4,000 infants. The de122q11 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 de122q11 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 de122q11 individuals. These genetic data in mouse, fish and human indicate that VEGF is a modifier of cardiovascular birth defects in the de122q11 syndrome.

Original languageEnglish (US)
Pages (from-to)173-182
Number of pages10
JournalNature Medicine
Issue number2
StatePublished - Feb 1 2003

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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