VEGF: a modifier of the del22q11 (DiGeorge) syndrome?

Nat Med. 2003 Feb;9(2):173-82. doi: 10.1038/nm819. Epub 2003 Jan 21.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Vessels / abnormalities
  • Chromosome Deletion*
  • Congenital Abnormalities / genetics
  • DiGeorge Syndrome / genetics*
  • Endothelial Growth Factors / genetics*
  • Face / abnormalities
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Lymphokines / genetics*
  • Mice
  • Mice, Knockout
  • Neuropilin-1 / genetics
  • Protein Isoforms / genetics
  • Skull / abnormalities
  • T-Box Domain Proteins / genetics
  • Thymus Gland / abnormalities
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Zebrafish


  • Endothelial Growth Factors
  • Intercellular Signaling Peptides and Proteins
  • Lymphokines
  • Protein Isoforms
  • T-Box Domain Proteins
  • Tbx1 protein, mouse
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Neuropilin-1