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 Conway, Peter Carmeliet

Research output: Contribution to journalArticle

226 Citations (Scopus)

Abstract

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
Volume9
Issue number2
DOIs
StatePublished - Feb 1 2003
Externally publishedYes

Fingerprint

DiGeorge Syndrome
Vascular Endothelial Growth Factor A
Defects
Blood Vessels
Branchial Region
Haploinsufficiency
Chromosome Deletion
Zebrafish
Haplotypes
Arches
Chromosomes
Protein Isoforms
Fishes
Fish
Embryonic Structures
Arteries

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Stalmans, I., Lambrechts, D., De Smet, F., Jansen, S., Wang, J., Maity, S., ... Carmeliet, P. (2003). VEGF: A modifier of the de122q11 (DiGeorge) syndrome? Nature Medicine, 9(2), 173-182. https://doi.org/10.1038/nm819

VEGF : A modifier of the de122q11 (DiGeorge) syndrome? / Stalmans, Ingeborg; Lambrechts, Diether; De Smet, Frederik; Jansen, Sandra; Wang, Jian; Maity, Sunit; Kneer, Paige; Der Ohe, Maren Von; Swillen, Ann; Maes, Christa; Gewillig, Marc; Molin, Daniel G M; Hellings, Peter; Boetel, Thurid; Haardt, Maartin; Compernolle, Veerle; Dewerchin, Mieke; Plaisance, Stephane; Vlietinck, Robert; Emanuel, Beverly; Gittenberger-de Groot, Adriana C.; Scambler, Peter; Morrow, Bernice; Driscol, Deborah A.; Moons, Lieve; Esguerra, Camila V.; Carmeliet, Geert; Behn-Krappa, Annett; Devriendt, Koen; Collen, Désiré; Conway, Simon; Carmeliet, Peter.

In: Nature Medicine, Vol. 9, No. 2, 01.02.2003, p. 173-182.

Research output: Contribution to journalArticle

Stalmans, I, Lambrechts, D, De Smet, F, Jansen, S, Wang, J, Maity, S, Kneer, P, Der Ohe, MV, Swillen, A, Maes, C, Gewillig, M, Molin, DGM, Hellings, P, Boetel, T, Haardt, M, Compernolle, V, Dewerchin, M, Plaisance, S, Vlietinck, R, Emanuel, B, Gittenberger-de Groot, AC, Scambler, P, Morrow, B, Driscol, DA, Moons, L, Esguerra, CV, Carmeliet, G, Behn-Krappa, A, Devriendt, K, Collen, D, Conway, S & Carmeliet, P 2003, 'VEGF: A modifier of the de122q11 (DiGeorge) syndrome?', Nature Medicine, vol. 9, no. 2, pp. 173-182. https://doi.org/10.1038/nm819
Stalmans I, Lambrechts D, De Smet F, Jansen S, Wang J, Maity S et al. VEGF: A modifier of the de122q11 (DiGeorge) syndrome? Nature Medicine. 2003 Feb 1;9(2):173-182. https://doi.org/10.1038/nm819
Stalmans, Ingeborg ; Lambrechts, Diether ; De Smet, Frederik ; Jansen, Sandra ; Wang, Jian ; Maity, Sunit ; Kneer, Paige ; Der Ohe, Maren Von ; Swillen, Ann ; Maes, Christa ; Gewillig, Marc ; Molin, Daniel G M ; Hellings, Peter ; Boetel, Thurid ; Haardt, Maartin ; Compernolle, Veerle ; Dewerchin, Mieke ; Plaisance, Stephane ; Vlietinck, Robert ; Emanuel, Beverly ; Gittenberger-de Groot, Adriana C. ; Scambler, Peter ; Morrow, Bernice ; Driscol, Deborah A. ; Moons, Lieve ; Esguerra, Camila V. ; Carmeliet, Geert ; Behn-Krappa, Annett ; Devriendt, Koen ; Collen, Désiré ; Conway, Simon ; Carmeliet, Peter. / VEGF : A modifier of the de122q11 (DiGeorge) syndrome?. In: Nature Medicine. 2003 ; Vol. 9, No. 2. pp. 173-182.
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