Martin Paul T
Center for Gene Therapy, Columbus Children's Research Institute, Departments of Pediatrics and Neurology, Ohio State University College of Medicine and Public Health, Columbus, OH 43205, USA.
Semin Pediatr Neurol. 2005 Sep;12(3):152-8. doi: 10.1016/j.spen.2005.10.003.
It has become clear in the past half decade that a number of forms of congenital muscular dystrophy are in fact congenital disorders of glycosylation. Genes for Walker Warburg syndrome, muscle-eye-brain disease, Fukuyama congenital muscular dystrophy, congenital muscular dystrophy 1C and 1D, and limb girdle muscular dystrophy 21 have been identified, and gene mutations resulting in these diseases all cause the underglycosylation of alpha dystroglycan with O-linked carbohydrates. Unlike congenital disorders of glycosylation involving the N-linked pathway, these O-linked disorders possess distinctive muscle, eye, and brain phenotypes. Studies using mice and patient tissues strongly suggest that underglycosylation of dystroglycan inhibits the binding extracellular matrix proteins, effectively divorcing this important cell adhesion molecule from its extracellular environment. Moreover, defects in dystroglycan alone can account for most, if not all, cellular pathology. Thus, these disorders are now collectively referred to as dystroglycanopathies.
在过去的五年里，已经很清楚的是，一些形式的先天性肌营养不良实际上是糖基化先天性疾病。沃克-沃尔堡综合征、肌肉-眼-脑疾病、福山先天性肌营养不良、先天性肌营养不良1C和1D以及肢带型肌营养不良21的相关基因已被确定，导致这些疾病的基因突变均会引起α-肌营养不良蛋白O-连接碳水化合物的糖基化不足。与涉及N-连接途径的糖基化先天性疾病不同，这些O-连接疾病具有独特的肌肉、眼睛和脑表型。使用小鼠和患者组织进行的研究强烈表明，肌营养不良蛋白糖基化不足会抑制其与细胞外基质蛋白的结合，有效地使其这个重要的细胞粘附分子与其细胞外环境分离。此外，仅肌营养不良蛋白的缺陷就可以解释大部分（如果不是全部）细胞病理学现象。因此，这些疾病现在统称为肌营养不良蛋白病。
