Glypican 3 and glypican 4 are juxtaposed in Xq26.1

Recently, we have shown that mutations in the X-linked glypican 3 (GPC3) ge ne 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. O ne recovered GPC4 cDNA with an open reading frame of 1668 nt encodes a puta tive protein containing three heparan sulfate glycosylation signals and the 14 signature cysteines of the glypican family. This protein is 94.3% ident ical to mouse GPC4 and 26% identical to human GPC3. In contrast to GPC3, wh ich produces a single transcript of 2.3 kb and is stringently restricted in expression to predominantly mesoderm-derived tissues, Northern analyses sh ow that GPC4 produces two transcripts, 3.4 and 4.6 kb, which are very widel y expressed (though at a much higher level in fetal lung and kidney). Inter estingly, of 20 SGBS patients who showed deletions in GPC3, one was also de leted for part of GPC4. Thus, GPC4 is not required for human viability, eve n in the absence of GPC3. This patient shows a complex phenotype, including the unusual feature of hydrocephalus; but because an uncle with SGBS is le ss affected, it remains unclear whether the GPC4 deletion itself contribute s to the phenotype. (C) 1998 Elsevier Science B.V. All rights reserved.