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 Emanuel; Adriana 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

doi:10.1038/nm819

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

Genetics

Research output: Contribution to journal › Article › peer-review

261 Scopus citations

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 language	English (US)
Pages (from-to)	173-182
Number of pages	10
Journal	Nature Medicine
Volume	9
Issue number	2
DOIs	https://doi.org/10.1038/nm819
State	Published - Feb 1 2003

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

Access to Document

10.1038/nm819

Cite this

Stalmans, I., Lambrechts, D., De Smet, F., Jansen, S., Wang, J., Maity, S., Kneer, P., Der Ohe, M. V., Swillen, A., Maes, C., Gewillig, M., Molin, D. G. M., Hellings, P., Boetel, T., Haardt, M., Compernolle, V., Dewerchin, M., Plaisance, S., Vlietinck, R., ... Carmeliet, P. (2003). VEGF: A modifier of the de122q11 (DiGeorge) syndrome? Nature Medicine, 9(2), 173-182. https://doi.org/10.1038/nm819

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, SJ & 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

@article{5704f8b869bc41a4ac07b55ae5fe4ea0,

title = "VEGF: A modifier of the de122q11 (DiGeorge) syndrome?",

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.",

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

year = "2003",

month = feb,

day = "1",

doi = "10.1038/nm819",

language = "English (US)",

volume = "9",

pages = "173--182",

journal = "Nature Medicine",

issn = "1078-8956",

publisher = "Nature Publishing Group",

number = "2",

}

TY - JOUR

T1 - VEGF

T2 - A modifier of the de122q11 (DiGeorge) syndrome?

AU - Stalmans, Ingeborg

AU - Lambrechts, Diether

AU - De Smet, Frederik

AU - Jansen, Sandra

AU - Wang, Jian

AU - Maity, Sunit

AU - Kneer, Paige

AU - Der Ohe, Maren Von

AU - Swillen, Ann

AU - Maes, Christa

AU - Gewillig, Marc

AU - Molin, Daniel G.M.

AU - Hellings, Peter

AU - Boetel, Thurid

AU - Haardt, Maartin

AU - Compernolle, Veerle

AU - Dewerchin, Mieke

AU - Plaisance, Stephane

AU - Vlietinck, Robert

AU - Emanuel, Beverly

AU - Gittenberger-de Groot, Adriana C.

AU - Scambler, Peter

AU - Morrow, Bernice

AU - Driscol, Deborah A.

AU - Moons, Lieve

AU - Esguerra, Camila V.

AU - Carmeliet, Geert

AU - Behn-Krappa, Annett

AU - Devriendt, Koen

AU - Collen, Désiré

AU - Conway, Simon J.

AU - Carmeliet, Peter

PY - 2003/2/1

Y1 - 2003/2/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0037329890&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037329890&partnerID=8YFLogxK

U2 - 10.1038/nm819

DO - 10.1038/nm819

M3 - Article

C2 - 12539040

AN - SCOPUS:0037329890

SN - 1078-8956

VL - 9

SP - 173

EP - 182

JO - Nature Medicine

JF - Nature Medicine

IS - 2

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this