MUTATIONS IN GPC3, A GLYPICAN GENE, CAUSE THE SIMPSON-GOLABI-BEHMEL OVERGROWTH SYNDROME

Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked condition charact erized by pre- and postnatal overgrowth with visceral and skeletal ano malies, To identify the causative gene, breakpoints in two female pati ents with X;autosome translocations were identified. The breakpoints o ccur near the 5' and 3' ends of a gene, GPC3, that spans more than 500 kilobases in Xq26; in three families, different microdeletions encomp assing exons cosegregate with SGBS. GPC3 encodes a putative extracellu lar proteoglycan, glypican 3, that is inferred to play an important ro le in growth control in embryonic mesodermal tissues in which it is se lectively expressed. Initial western- and ligand-blotting experiments suggest that glypican 3 forms a complex with insulin-like growth facto r 2 (IGF2), and might thereby modulate IGF2 action.