Glypican 3 and glypican 4 are juxtaposed in Xq26.1

• Published in: Gene Vol. 225; no. 1; pp. 9 - 16
• Main Authors: Huber, Reid, Mazzarella, Richard, Chen, Chun-Nan, Chen, Ellson, Ireland, Maggie, Lindsay, Susan, Pilia, Giuseppe, Crisponi, Laura
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 28-12-1998
• Subjects: Abnormalities, Multiple - genetics; Amino Acid Sequence; Animals; Base Sequence; Centromere; DNA - genetics; Gene Expression Regulation, Developmental; Glypicans; Heparan Sulfate Proteoglycans - genetics; Heparitin Sulfate - genetics; Humans; Mice; Molecular Sequence Data; Physical Chromosome Mapping; Proteoglycan; Proteoglycans - genetics; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sequence Alignment; Sequence Deletion; Sequence Homology, Amino Acid; Simpson–Golabi–Behmel Syndrome; Tissue Distribution; Transcription, Genetic; Tumor Cells, Cultured; X chromosome; X Chromosome - genetics; Proteoglycan; GPC3, glypican 3; SGBS, Simpson–Golabi–Behmel Syndrome; GPC4, glypican 4; Simpson–Golabi–Behmel Syndrome; X chromosome
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/S0378-1119(98)00549-6

Recently, we have shown that mutations in the X-linked glypican 3 (
GPC3) gene cause the Simpson–Golabi–Behmel overgrowth syndrome (SGBS;
Pilia et al., 1996). The next centromeric gene detected is another glypican, glypican 4 (
GPC4), with its 5′ end 120 763
bp downstream of the 3′ terminus of
GPC3. One recovered
GPC4 cDNA with an open reading frame of 1668
nt encodes a putative protein containing three heparan sulfate glycosylation signals and the 14 signature cysteines of the glypican family. This protein is 94.3% identical to mouse GPC4 and 26% identical to human GPC3. In contrast to
GPC3, which produces a single transcript of 2.3
kb and is stringently restricted in expression to predominantly mesoderm-derived tissues, Northern analyses show that
GPC4 produces two transcripts, 3.4 and 4.6
kb, which are very widely expressed (though at a much higher level in fetal lung and kidney). Interestingly, of 20 SGBS patients who showed deletions in
GPC3, one was also deleted for part of
GPC4. Thus,
GPC4 is not required for human viability, even in the absence of
GPC3. This patient shows a complex phenotype, including the unusual feature of hydrocephalus; but because an uncle with SGBS is less affected, it remains unclear whether the
GPC4 deletion itself contributes to the phenotype.