Isolation and characterization of a novel gene containing WD40 repeats from the region deleted in velo-cardio-facial/DiGeorge syndrome on chromosome 22q11

Three congenital disorders, cat-eye syndrome (CES), der(22) syndrome, and v elo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS), result from tetras omy, trisomy, and monosomy, respectively, of part of 22q11. They share a 1. 5-Mb region of overlap, which contains 24 known genes. Although the region has been sequenced and extensively analyzed, it is expected to contain addi tional genes, which have thus far:escaped identification. To understand com pletely the; molecular etiology of VCFS/DGS, der(22) syndrome,and CES, it i s essential to isolate all genes in the interval. We have identified and ch aracterized a novel human gene, located within the 1.5-Mb region deleted in VCFS/DGS, trisomic in der(22) syndrome and tetrasomic in CES. The deduced amino acid sequence of the human gene and its mouse homologue contain sever al WD40 repeats, but lack homology to known proteins. We termed this gene W DR14 (WD40 repeat-containing gene deleted in VCFS). It is expressed in a va riety of human and mouse adult and fetal tissues with substantial expressio n levels in the adult thymus, an organ hypoplastic in VCFS/DGS. (C) 2001 Ac ademic Press.