Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome.
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.
Pilia
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Center for Genetics in Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Hughes-Benzie
R M
RM
MacKenzie
A
A
Baybayan
P
P
Chen
E Y
EY
Huber
R
R
Neri
G
G
Cao
A
A
Forabosco
A
A
Schlessinger
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D
D000015:Abnormalities, Multiple / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002869:Chromosome Aberrations / Q000235:genetics*; D025063:Chromosome Disorders; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D002885:Chromosomes, Human, Pair 16; D003001:Cloning, Molecular; D017931:DNA Primers; D005260:Female; D017353:Gene Deletion; D008040:Genetic Linkage; D053673:Glypicans; D006130:Growth Disorders / Q000235:genetics*; D006367:HeLa Cells; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007158:Immunologic Techniques; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010375:Pedigree; D011485:Protein Binding; D011509:Proteoglycans / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013577:Syndrome; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured; D014960:X Chromosome
D017931:DNA Primers; D053673:Glypicans; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D007335:Insulin-Like Growth Factor II; D011509:Proteoglycans