ISOLATION OF A PUTATIVE TRANSCRIPTIONAL REGULATOR FROM THE REGION OF 22Q11 DELETED IN DIGEORGE-SYNDROME, SHPRINTZEN SYNDROME AND FAMILIAL CONGENITAL HEART-DISEASE

A wide spectrum of birth defects are caused by deletions of the DiGeor ge syndrome critical region (DGCR) at human chromosome 22q11. Over one hundred such deletions have now been examined and a minimally deleted region of 300kb defined. Within these sequences we have identified a gene expressed during human and murine embryogenesis. The gene, named TUPLE1, and its murine homologue, encodes a protein containing repeate d motifs similar to the WD40 domains found in the beta-transducin/enha ncer of split (TLE) family. The TUPLE1 product has several features ty pical of transcriptional control proteins and in particular has homolo gy with the yeast Tup1 transcriptional regulator. We propose that hapl oinsufficiency for TUPLE1 is at least partly responsible for DiGeorge syndrome and related abnormalities.