Genetic analysis of digeorge syndrome and related disorders

Since patients with DiGeorge syndrome (DGS) commonly have deletions of 22q11.2, haploinsufficiency of a certain gene(s) in this region is thought to cause the syndrome. The deletion is also seen in patients with other syndromes with cardiac anomaly and facial dysmorphism, suggesting that the syndromes are contiguous gene syndromes. We constructed two cosmid contigs in the deletion, which contained region specific repetitive sequences. The deletion map of the patients allowed us to identify three types of deletions. Most patients have apparently identical large interstitial deletions in spite of phenotypic variability, suggesting that at the breakpoint there exists a specific repetitive sequence prone to deletion. A unique deletion was identified, which did not contain the "shortest region of overlap". Subsequently, we isolated a novel cDNA located on one of the cosmid contigs. The cDNA was revealed to encode a transcriptional factor and to be expressed in vital fetal organs. Haploinsufficiency of the gene may be partly related to the development of the syndromes.