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) aredevelopmental disorders characterized by a spectrum of phenotypes includingvelopharyngeal insufficiency, conotruncal heart defects and facialdysmorphology among others. Eighty to eighty-five percent of VCFS/DGSpatients are hemizygous for a portion of chromosome 22. It is likely thatthe genes encoded by this region play a role in the etiology of thephenotypes associated with the disorders. Using a cDNA selection protocol,we isolated a novel clathrin heavy chain cDNA (CLTD) from the VCFS/DGSminimally deleted interval. The cDNA encodes a protein of 1638 amino acids.CLTD shares significant homology, but is not identical to the ubiquitouslyexpressed clathrin heavy chain gene. The CLTD gene also shows a uniquepattern of expression, having its maximal level of expression in skeletalmuscle. Velopharyngeal insufficiency and muscle weakness are commonfeatures of VCFS patients. Based on the location and expression pattern ofCLTD, we suggest hemizygosity at this locus may play a role in the etiologyof one of the VCFS-associated phenotypes.