ISOLATION OF A GENE ENCODING AN INTEGRAL MEMBRANE-PROTEIN FROM THE VICINITY OF A BALANCED TRANSLOCATION BREAKPOINT ASSOCIATED WITH DIGEORGE-SYNDROME

Deletions within 22q11 have been associated with a wide variety of bir th defects embraced by the acronym CATCH22 and including the DiGeorge syndrome, Shprintzen syndrome (velocardiofacial syndrome) and congenit al heart disease, It is not known how many genes contribute to this ph enotype, Previous studies have shown that a balanced translocation dis rupts sequences within the shortest region of deletion overlap for DiG eorge syndrome, A P1 clone was isolated which spans this breakpoint an d used to isolate a cDNA encoding a transmembrane protein expressed in a wide variety of tissues, This gene (called IDD) is not disrupted by the translocation, but maps within 10 kb of the breakpoint, Mutation analysis of five affected cases with no previously identified chromoso me 22 deletion was negative; but a potential protein polymorphism was discovered, No deletions or rearrangements were detected in these pati ents following analysis with markers closely flanking the breakpoint, data which emphasize that large (i.e. over 1 Mb) interstitial deletion s are the rule in DiGeorge syndrome, The proximity of IDD to the balan ced translocation breakpoint and its position within the shortest regi on of deletion overlap indicate that this gene may have a role, along with other genes, in the CATCH22 haploinsufficiency syndromes.