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

I. Stalmans, D. Lambrechts, F. de Smet, S. Jansen, J. Wang, S. Maity, P. Kneer, M. von der Ohe, A. Swillen, C. Maes, M. Gewillig, D.G.M. Molin, P. Hellings, T. Boetel, M. Haardt, V. Compernolle, M. Dewerchin, S. Plaisance, R.F.M. Vlietinck, al. etSimon J. Conway *

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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

Stalmans I, Lambrechts D, De Smet F, Jansen S, Wang J, Maity S, Kneer P, von der Ohe M, Swillen A, Maes C, Gewillig M, Molin DG, 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 SJ, Carmeliet P.

The Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Katholieke Universiteit Leuven, Leuven, Belgium.

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.

Original languageEnglish
Pages (from-to)173-182
Number of pages5
JournalNature Medicine
Issue number2
Publication statusPublished - 1 Jan 2003

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