Nature Genetics
12, 241 - 247 (1996)
doi:10.1038/ng0396-241
Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndromeGiuseppe Pilia1, 5, Rhiannon M. Hughes-Benzie2, Alex MacKenzie2, Primo Baybayan3, Ellson Y. Chen3, Reid Huber1, Giovanni Neri4, Antonio Cao5, Antonino Forabosco6
& David Schlessinger1
1Center for Genetics in Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
2Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Canada K1H 8L1.
3Advanced Center for Genetic Technology, Applied Biosystems Division of Perkin-Elmer Corporation, Foster City, California 94404.
4Istituto di Genetica Umana, Catholic University, Rome, Italy 00168.
5Istituto di Clinica e Biologia dell'Eta Evolutiva, University of Cagliari, ed Istituto di Ricerca sulle Talassemie e Anemie Mediterranee, Cagliari, Italy 09121.
6Dipartimento di Scienze Morfologiche e Medico Legali, University of Modena, Modena, Italy 41100. Correspondence should be addressed to D.S. Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked condition characterized by pre-and postnatal overgrowth with visceral and skeletal anomalies. To identify the causative gene, breakpoints in two female patients with X;autosome translocations were identified. The breakpoints occur near the 5', and 3', ends of a gene, GPC3, that spans more than 500 kilobases in Xq26; in three families, different microdeletions encompassing exons cosegregate with SGBS. GPC3 encodes a putative extracellular proteoglycan, glypican 3, that is inferred to play an important role in growth control in embryonic mesodermal tissues in which it is selectively expressed. Initial western- and ligand-blotting experiments suggest that glypican 3 forms a complex with insulin-like growth factor 2 (IGF2), and might thereby modulate IGF2 action.
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