缺陷的LARGE导致MDDGA6和MDDGB6
中文名称
通路描述
糖基转移酶样蛋白LARGE（MIM:603590）是一种双功能糖基转移酶，具有异戊基转移酶和β-1,3-葡萄糖醛酸转移酶活性，参与磷酸化O-甘露糖三聚糖的生物合成，该结构存在于α- dystroglycan（DAG1; MIM:128239）中，后者在骨骼肌功能和再生中起关键作用。LARGE含有两个底物特异性GT结构域，属于CAZy糖基转移酶家族GT8和GT49。LARGE的缺陷导致DAG1的糖基化降低，并导致几种先天性肌营养不良症（CMDs）。肌肉 dystrophy-dystroglycanopathy 先天性伴脑和眼异常A6（MDDGA6; MIM:613154）与脑异常、眼畸形、严重智力障碍和通常在生命早期死亡相关（Clement et al. 2008, Mercuri et al. 2009）。肌肉 dystrophy-dystroglycanopathy 先天性伴智力障碍B6（MDDGB6; MIM:608840）与严重智力障碍、白质改变和结构性脑异常相关（Longman et al. 2003）。
英文描述
Defective LARGE causes MDDGA6 and MDDGB6 Glycosyltransferase-like protein LARGE (MIM:603590) is a bifunctional glycosyltransferase with both xylosyltransferase and beta-1,3-glucuronyltransferase activities involved in the biosynthesis of a phosphorylated O-mannosyl trisaccharide, a structure present in alpha-dystroglycan (DAG1; MIM:128239) which plays a key role in skeletal muscle function and regeneration. LARGE contains two substrate-specific GT-domains and belongs to the CAZy glycosyltransferase families GT8 and GT49. Defects in LARGE result in hypoglycosylation of DAG1 and cause several congenital muscular dystrophies (CMDs). Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A6 (MDDGA6; MIM:613154) is associated with brain anomalies, eye malformations, profound mental retardation, and death usually in the first years of life (Clement et al. 2008, Mercuri et al. 2009). Muscular dystrophy-dystroglycanopathy congenital with mental retardation B6 (MDDGB6; MIM:608840) is associated with profound mental retardation, white matter changes and structural brain abnormalities (Longman et al. 2003).
所含基因
1 个基因