Medical Genetics Unit, Centre Hospitalier Universitaire d'Amiens, Amiens, France.
Am J Med Genet A. 2014 Mar;164A(3):774-7. doi: 10.1002/ajmg.a.36335. Epub 2013 Dec 19.
Simpson-Golabi-Behmel syndrome type 1 (SGBS1) -OMIM 312870- is a rare X-linked inherited overgrowth syndrome caused by a loss of function mutation in the GPC3 gene. Affected patients present a variable phenotype with pre- and post-natal macrosomia, distinctive facial dysmorphism, organomegaly, and multiple congenital anomalies. Intellectual disability is not constant. About 10% of patients have an increased risk of developing embryonic tumors in early childhood. Only one case of biliary disease has been described so far. GPC3 is localized on Xq26. It encodes for glypican 3, a heparan sulfate proteoglycan, which among its different known roles, negatively regulates liver regeneration and hepatocyte proliferation. This report concerns a male with a SGBS1, carrier of a GPC3 pathogenic mutation, and neonatal liver disease, who developed an early biliary cirrhosis. Together with the associated risk of cancer and developmental delay, liver transplantation was discussed and then successfully performed at the age of 19 months. A hypothesis on the role of GPC3 in the patient's liver disease is also proposed.
Simpson-Golabi-Behmel 综合征 1 型（SGBS1）-OMIM 312870-是一种罕见的 X 连锁遗传性过度生长综合征，由 GPC3 基因的功能丧失突变引起。受影响的患者表现出不同的表型，包括产前和产后巨大儿、独特的面部畸形、器官肿大和多种先天性异常。智力残疾并非一成不变。约 10%的患者在幼儿期有发生胚胎肿瘤的风险增加。到目前为止，只有一例胆道疾病的描述。GPC3 定位于 Xq26。它编码聚糖蛋白 3，一种硫酸乙酰肝素蛋白聚糖，在其已知的不同作用中，它负向调节肝脏再生和肝细胞增殖。本报告涉及一名男性，患有 SGBS1，携带 GPC3 致病性突变，并患有新生儿期肝病，他在早期发展为胆汁性肝硬化。结合癌症和发育迟缓的相关风险，讨论了肝移植，并在 19 个月大时成功进行了肝移植。还提出了关于 GPC3 在患者肝病中的作用的假设。
