缺陷的EXT1导致骨外生骨疣1、TRPS2和CHDS
中文名称
通路描述
缺陷的EXT1导致骨外生骨疣1、TRPS2和CHDS。肝素硫酸（HS）在发育、稳态和病理过程中调节各种身体功能，包括凝血、血管生成和癌细胞转移。外泌素1和2（EXT1和2）糖基转移酶是形成HS所必需的。它们能够在HS合成期间将N-乙酰葡萄糖胺（GlcNAc）和葡萄糖醛酸（GlcA）转移到HS上。这些酶的功能形式似乎是两个酶在高尔基体膜上的复合物。EXT1或EXT2的缺陷可导致遗传性多骨外生骨疣1（Petersen 1989）和2（McGaughran et al. 1995）（MIM:133700和MIM:133701），这是一种常染色体显性遗传病，其特征为多发性骨外生骨疣，骨端被软骨覆盖，导致腿、前臂和手部畸形。三叉颅面骨发育异常综合征，类型II（TRPS2，也称为Langer-Giedion综合征，LGS）是一种疾病，其特征为三叉颅面骨发育异常综合征类型I（TRPS1, MIM:190350）和骨外生骨疣类型I的临床特征相结合，由TRPS1和EXT1基因突变引起（Langer et al. 1984, Ludecke et al. 1995）。EXT1的缺陷也可能与软骨肉瘤（CHDS; MIM:215300）有关（Schajowicz & Bessone 1967, Hecht et al. 1995）。
英文描述
Defective EXT1 causes exostoses 1, TRPS2 and CHDS Heparan sulfate (HS) is involved in regulating various body functions functions during development, homeostasis and pathology including blood clotting, angiogenesis and metastasis of cancer cells. Exostosin 1 and 2 (EXT1 and 2) glycosyltransferases are required to form HS. They are able to transfer N-acetylglucosamine (GlcNAc) and glucuronate (GlcA) to HS during its synthesis. The functional form of these enzymes appears to be a complex of the two located on the Golgi membrane. Defects in either EXT1 or EXT2 can cause hereditary multiple exostoses 1 (Petersen 1989) and 2 (McGaughran et al. 1995) respectively (MIM:133700 and MIM:133701), autosomal dominant disorders characterized by multiple projections of bone capped by cartilage resulting in deformed legs, forearms and hands. Trichorhinophalangeal syndrome, type II (TRPS2 aka Langer-Giedion syndrome, LGS) is a disorder that combines the clinical features of trichorhinophalangeal syndrome type I (TRPS1, MIM:190350) and multiple exostoses type I, caused by mutations in the TRPS1 and EXT1 genes, respectively (Langer et al. 1984, Ludecke et al. 1995). Defects in EXT1 may also be responsible for chondrosarcoma (CHDS; MIM:215300) (Schajowicz & Bessone 1967, Hecht et al. 1995).
所含基因
2 个基因