GPC4,the Gene for Human K-Glypican, FlanksGPC3on Xq26: Deletion of theGPC3–GPC4Gene Cluster in One Family with Simpson–Golabi–Behmel Syndrome

The glypicans constitute a growing family of cell surface heparan sulfate proteoglycans that may play a role in the control of cell division and growth regulation. Recently, deletions and translocations involvingGPC3(the gene for glypican-3, localized on Xq26) have been identified in patients with Simpson–Golabi–Behmel syndrome (SGBS). This X-linked syndrome is characterized by pre- and postnatal overgrowth, visceral and skeletal abnormalities, and a high risk for the development of embryonal tumors, mostly Wilms tumor and neuroblastoma. In the present report we show that the gene for human K-glypican/glypican-4 (GPC4) also maps to Xq26, centromeric toGPC3. The glypican-4 protein is encoded by nine exons. Establishment of a BAC/PAC contig physically linkingGPC4andGPC3indicates that these two genes are arranged in a tandem array, the 5′ end ofGPC4flanking the 3′ end ofGPC3. Unlike the glypican-3 message, the glypican-4 message is nearly ubiquitous. Analysis of DNA samples from eight patients with diagnosis of SGBS identified one individual with a deletion that involves the entireGPC4gene and the last two exons ofGPC3.The tight clustering ofGPC3andGPC4,with deletions that occasionally affect both genes, may be relevant for explaining the variability of the SGBS phenotype.