CONGENITAL HEART-DEFECTS AND 22Q11 DELETIONS - WHICH GENES COUNT

Hemizygous deletions on the long arm of chromosome 22 (del22q11) are a relatively common cause of congenital heart disease. For some specifi c heart defects such as interrupted aortic arch type B and tetralogy o f Fallot with absent pulmonary valve, del22q11 is probably the most fr equent genetic cause. Although extensive gene searches have been succe ssful in discovering many novel genes in the deleted segment, standard positional cloning has so far failed to demonstrate a role for any of these genes in the disease. We show how the use of experimental anima l models is beginning to provide an insight into the developmental rol e of some of these genes, while novel genome manipulation technologies promise to dissect the genetic aspects of this complex syndrome.