Vaisfeld Alessandro, Neri Giovanni
Medical Genetics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
Am J Med Genet C Semin Med Genet. 2024 Dec;196(4):e32088. doi: 10.1002/ajmg.c.32088. Epub 2024 May 20.
The Simpson-Golabi-Behmel syndrome (SGBS; OMIM 312870) is an overgrowth/multiple congenital anomalies/dysplasia condition, inherited as an X-linked semi-dominant trait, with variable expressivity in males and reduced penetrance and expressivity in females. The clinical spectrum is broad, ranging from mild manifestations in both males and females to multiple malformations and neonatal death in the more severely affected cases. An increased risk of neoplasia is reported, requiring periodical surveillance. Intellectual development is normal in most cases. SGBS is caused by a loss-of-function mutation of the GPC3 gene, either deletions or point mutations, distributed all over the gene. Notably, GPC3 deletion/point mutations are not found in a significant proportion of clinically diagnosed SGBS cases. The protein product GPC3 is a glypican functioning as a receptor for Hh at the cell surface, involved in the Hh-Ptc-Smo signaling pathway, a regulator of cellular growth.
辛普森-戈拉比-贝梅尔综合征（SGBS；OMIM 312870）是一种过度生长/多发先天性异常/发育异常疾病，呈X连锁半显性遗传，男性表现度可变，女性外显率和表现度降低。临床谱广泛，从男性和女性的轻度表现到病情较重病例的多种畸形和新生儿死亡。据报道肿瘤形成风险增加，需要定期监测。大多数病例智力发育正常。SGBS由GPC3基因功能丧失性突变引起，包括基因各处的缺失或点突变。值得注意的是，在相当比例的临床诊断SGBS病例中未发现GPC3缺失/点突变。蛋白质产物GPC3是一种硫酸乙酰肝素蛋白聚糖，在细胞表面作为Hh的受体发挥作用，参与Hh-Ptc-Smo信号通路，该通路是细胞生长的调节因子。
