Journal article Open Access
Huber, Reid; Mazzarella, Richard; Chen, Chun-Nan; Chen, Ellson; Ireland, Maggie; Lindsay, Susan; Pilia, Giuseppe; Crisponi, Laura
Recently, we have shown that mutations in the X-linked glypican 3 (GPC3) gene cause the Simpson-Golabi-Behmel overgrowth syndrome (SGBS; ). The next centromeric gene detected is another glypican, glypican 4 (GPC4), with its 5' end 120763bp downstream of the 3' terminus of GPC3. One recovered GPC4 cDNA with an open reading frame of 1668nt 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 2.3kb and is stringently restricted in expression to predominantly mesoderm-derived tissues, Northern analyses show that GPC4 produces two transcripts, 3.4 and 4.6kb, 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.