IDENTIFICATION OF A NEW HUMAN CATENIN GENE FAMILY MEMBER (ARVCF) FROMTHE REGION DELETED IN VELO-CARDIO-FACIAL SYNDROME

Velo-cardio-facial syndrome (VCFS) and DiGeorge syndrome (DCS) are cha racterized by a wide spectrum of phenotypes, including conotruncal hea rt defects, cleft palate, and facial dysmorphology. Hemizygosity for a portion of chromosome 22q11 has been detected in 80-85% of VCFS/DGS p atients. Both syndromes are thought to be the result of a developmenta l field defect. Using two independent gene isolation procedures, we is olated a new catenin family member termed ARVCF (armadillo repeat gene deleted in VCFS) from the interval deleted in VCFS. ARVCF encodes a p rotein of 962 amino acids that contains a coiled coil domain and 10 ta ndem armadillo repeats. The primary structure of the protein is most c losely related to the murine catenin p120(CAS), which suggests a role for ARVCF in protein-protein interactions at adherens junctions. ARVCF is expressed ubiquitously in all fetal and adult tissues examined. Th is gene is hemizygous in all VCFS patients with interstitial deletions . Based on the physical location and potential functions of ARVCF, we suggest that hemizygosity at this locus may play a role in the etiolog y of some of the phenotypes associated with VCFS. (C) 1997 Academic Pr ess.