Genetic Defects Traced in DiGeorge Syndrome

Their findings were reported in the February 2003 issue of Nature Medicine.

DiGeorge syndrome can cause a wide range of heart defects, many of which are vascular in nature, as well as problems with the thymus and parathyroid gland, craniofacial abnormalities, and mental retardation.

The genome of 60-70% of victims of DiGeorge syndrome lacks chromosome 22, which represents a loss of a group of 24 genes. One of these genes, Tbx1, had been considered to be the primary gene involved in DiGeorge syndrome. Researchers from the Medical College of Georgia (Augusta, USA; www.mcg.edu) and Catholic University Leuven (Belgium; www.leuven.ac.be) realized that the wide variety of syndromes presented by sufferers implied the role of other genes, such as that for VEGF.

"It struck us that in the mouse model for DiGeorge syndrome, a lot of the heart defects are vascular in nature, so we looked at one of the major vascular genes, VEGF,” explained senior American investigator Dr. Simon J. Conway, a developmental biologist at the Medical College of Georgia. "If you knock out VEGF from a mouse model, it dies very, very early, before you get a heart, a head, even before you see an embryo proper.”

Working with a VEGF knockout mouse developed by the Belgian group, the investigators found that only the 164/164 form of the VEGF gene was critical to the development of DiGeorge syndrome. Mice lacking this gene developed symptoms similar to DiGeorge syndrome. Dr. Conway explained that something on chromosome 22 was working with VEGF, and that it probably was Tbx1, and that a reduction in Tbx1 and a corresponding reduction in VEGF were enough to produce DiGeorge syndrome.





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Medical College of Georgia
Catholic University Leuven