ISOLATION OF A NEW CLATHRIN HEAVY-CHAIN GENE WITH MUSCLE-SPECIFIC EXPRESSION FROM THE REGION COMMONLY DELETED IN VELO-CARDIO-FACIAL SYNDROME

Velo-cardio-facial syndrome (VCFS) and DiGeorge syndrome (DGS) are dev elopmental disorders characterized by a spectrum of phenotypes includi ng velopharyngeal insufficiency, conotruncal heart defects and facial dysmorphology among others, Eighty to eighty-five percent of VCFS/DGS patients are hemizygous for a portion of chromosome 22. It is likely t hat the genes encoded by this region play a role in the etiology of th e phenotypes associated with the disorders, Using a cDNA selection pro tocol, we isolated a novel clathrin heavy chain cDNA (CLTD) from the V CFS/DGS minimally deleted interval, The cDNA encodes a protein of 1638 amino acids, CLTD shares significant homology, but is not identical t o the ubiquitously expressed clathrin heavy chain gene, The CLTD gene also shows a unique pattern of expression, having its maximal level of expression in skeletal muscle, Velopharyngeal insufficiency and muscl e weakness are common features of VCFS patients, Based on the location and expression pattern of CLTD, we suggest hemizygosity at this locus may play a role in the etiology of one of the VCFS-associated phenoty pe.