The 22q11 deletion syndromes

DiGeorge syndrome, velocardiofacial syndrome and various other malformation s have been described in association with deletions and translocations invo lving human chromosome 22q11. Many of the structural malformations observed are also seen in animal models of neural crest disruption suggesting that the haplo-insufficiency resulting from the deletion somehow affects this gr oup of cells or their interactions. Over the past few years it has been sho wn that the deletion predisposes to a range of psychotic conditions prompti ng the hypothesis that the deleted region may contain a predisposition locu s for psychotic illness. The DiGeorge chromosomal region has been entirely sequenced and many of the genes mapping to the deletion interval have been studied in some detail. Despite these efforts, no gene has yet been proved to play a defined role in the pathogenesis of the syndrome. Current efforts are directed at the study of engineered chromosome mouse models which offe r the potential to dissect at least some of the developmental pathways disr upted in this intriguing group of malformation syndromes.