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 developmental disorders characterized by a spectrum of phenotypes including 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 that the genes encoded by this region play a role in the etiology of the phenotypes associated with the disorders. Using a cDNA selection protocol, we isolated a novel clathrin heavy chain cDNA (CLTD) from the VCFS/DGS minimally deleted interval. The cDNA encodes a protein of 1638 amino acids. CLTD shares significant homology, but is not identical to 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 muscle 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 phenotypes.      

Type IIB Tampa: a variant of von Willebrand disease with chronic thrombocytopenia, circulating platelet aggregates, and spontaneous platelet aggregation

Type IIB von Willebrand disease is characterized by enhanced ristocetin- induced platelet aggregation and absence of large von Willebrand factor multimers from plasma. An alteration of the von Willebrand factor molecule resulting in increased reactivity with platelets appears to be the basis for these abnormalities. We have now identified a new variant of type IIB von Willebrand disease in a family in which the four affected members also have chronic thrombocytopenia, in vivo platelet aggregate formation, and spontaneous platelet aggregation in vitro. In spite of repeatedly prolonged bleeding times and persistent thrombocytopenia, their bleeding diathesis is only moderate.     

Splanchnic artery aneurysms and pseudoaneurysms: transcatheter embolization

Over the past 7 years, eight patients with splanchnic artery aneurysms and pseudoaneurysms were studied and treated. Transcatheter embolization resulted in occlusion of the lesions in all eight patients. Potentially risky and difficult surgery was avoided completely in four patients. Three patients had elective surgery at a later date when their condition was more stable. The remaining patient had definitive surgery after embolization. Transcatheter embolization should be the initial treatment of choice in splanchnic artery aneurysms and pseudoaneurysms.