Dubowitz Neuromuscular Centre, UCL Institute of Child Health and Great Ormond Street Hospital, London, UK.
Curr Opin Neurol. 2011 Oct;24(5):437-42. doi: 10.1097/WCO.0b013e32834a95e3.
Dystroglycanopathies are a common group of diseases characterized by a reduction in α-dystroglycan glycosylation. This review discusses the recent novel discovery of additional dystroglycanopathy variants and progress in dystroglycanopathy animal models.
Several novel glycosyltransferase genes have been found to be responsible for a dystroglycanopathy phenotype, and in addition recessive mutations in DAG1 have been identified for the first time in a primary dystroglycanopathy. Studies in dystroglycanopathy mouse models have clarified some aspects of the structural defects observed in the central nervous system and in the eye, whereas a study in zebrafish implicates unfolded protein response in the pathogenesis of two of the secondary dystroglycanopathies.
Improved understanding of the molecular bases of dystroglycanopathies will lead to more precise diagnosis and genetic counseling; therapeutic strategies are being developed and tested in the preclinical models and it is hoped that these observations will pave the way to therapeutic interventions in humans.
肌营养不良聚糖病是一组常见的疾病，其特征是α- 肌营养不良聚糖减少。本综述讨论了最近发现的肌营养不良聚糖病新变体和肌营养不良聚糖病动物模型的进展。
已经发现了几个新的糖基转移酶基因负责肌营养不良聚糖病的表型，并且首次在原发性肌营养不良聚糖病中发现 DAG1 基因的隐性突变。肌营养不良聚糖病小鼠模型的研究澄清了中枢神经系统和眼睛中观察到的结构缺陷的一些方面，而斑马鱼的一项研究表明未折叠蛋白反应参与了两种继发性肌营养不良聚糖病的发病机制。
对肌营养不良聚糖病分子基础的深入了解将导致更精确的诊断和遗传咨询；治疗策略正在临床前模型中进行开发和测试，希望这些观察结果将为人类的治疗干预铺平道路。
