In the family reported by Golabi and Rosen, a duplication of GPC4 was recently identified, suggesting that GPC4 could be the second gene for SGBS but no point mutations within GPC4 have yet been reported.
Analysis of DNA samples from eight patients with diagnosis of SGBS identified one individual with a deletion that involves the entire GPC4 gene and the last two exons of GPC3.
One region of Xq26.2 comprises the genes GPC3 and GPC4; deletion or duplication of this region has been recently been shown to result in overgrowth, specifically Simpson-Golabi-Behmel syndrome.
GPC5 and GPC6 show homology with GPC3 and GPC4, genes involved in Simpson-Golabi-Behmel syndrome, an overgrowth syndrome in which also polydactyly can occur.
Phylogenetic analysis demonstrated that GPC4 is most closely related to GPC6, which is associated with a bone dysplasia that has a phenotypic overlap with Keipert syndrome.
Phylogenetic analysis demonstrated that GPC4 is most closely related to GPC6, which is associated with a bone dysplasia that has a phenotypic overlap with Keipert syndrome.
Phylogenetic analysis demonstrated that GPC4 is most closely related to GPC6, which is associated with a bone dysplasia that has a phenotypic overlap with Keipert syndrome.
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.