Veugelers M, Vermeesch J, Watanabe K, Yamaguchi Y, Marynen P, David G
Center for Human Genetics, University of Leuven, Leuven, B-3000, Belgium.
Genomics. 1998 Oct 1;53(1):1-11. doi: 10.1006/geno.1998.5465.
The glypicans constitute a growing family of cell surface heparan sulfate proteoglycans that may play a role in the control of cell division and growth regulation. Recently, deletions and translocations involving GPC3 (the gene for glypican-3, localized on Xq26) have been identified in patients with Simpson-Golabi-Behmel syndrome (SGBS). This X-linked syndrome is characterized by pre- and postnatal overgrowth, visceral and skeletal abnormalities, and a high risk for the development of embryonal tumors, mostly Wilms tumor and neuroblastoma. In the present report we show that the gene for human K-glypican/glypican-4 (GPC4) also maps to Xq26, centromeric to GPC3. The glypican-4 protein is encoded by nine exons. Establishment of a BAC/PAC contig physically linking GPC4 and GPC3 indicates that these two genes are arranged in a tandem array, the 5' end of GPC4 flanking the 3' end of GPC3. Unlike the glypican-3 message, the glypican-4 message is nearly ubiquitous. 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. The tight clustering of GPC3 and GPC4, with deletions that occasionally affect both genes, may be relevant for explaining the variability of the SGBS phenotype.
磷脂酰肌醇蛋白聚糖构成了一个不断增加的细胞表面硫酸乙酰肝素蛋白聚糖家族，可能在细胞分裂控制和生长调节中发挥作用。最近，在辛普森-戈拉比-贝梅尔综合征（SGBS）患者中发现了涉及GPC3（磷脂酰肌醇蛋白聚糖-3基因，定位于Xq26）的缺失和易位。这种X连锁综合征的特征是产前和产后过度生长、内脏和骨骼异常，以及胚胎肿瘤发生的高风险，主要是肾母细胞瘤和神经母细胞瘤。在本报告中，我们表明人类K-磷脂酰肌醇蛋白聚糖/磷脂酰肌醇蛋白聚糖-4（GPC4）基因也定位于Xq26，在GPC3的着丝粒侧。磷脂酰肌醇蛋白聚糖-4蛋白由九个外显子编码。建立物理连接GPC4和GPC3的BAC/PAC重叠群表明这两个基因以串联排列，GPC4的5'端位于GPC3的3'端侧翼。与磷脂酰肌醇蛋白聚糖-3信息不同，磷脂酰肌醇蛋白聚糖-4信息几乎无处不在。对八名诊断为SGBS的患者的DNA样本分析发现，有一名个体的缺失涉及整个GPC4基因和GPC3的最后两个外显子。GPC3和GPC4的紧密聚集，以及偶尔影响两个基因的缺失，可能与解释SGBS表型的变异性有关。
