Piccolo F, Moore S A, Ford G C, Campbell K P
Howard Hughes Medical Institute, Department of Physiology and Biophysics, University of Iowa College of Medicine, Iowa City 52242, USA.
Ann Neurol. 2000 Dec;48(6):902-12.
Dysferlin has recently been identified as a novel gene involved in limb-girdle muscular dystrophy type 2B (LGMD2B) and its allelic disease, Miyoshi myopathy. The predicted structure of dysferlin suggests that it is a transmembrane protein possibly involved in membrane fusion. Thus, unlike previously identified structural proteins in muscular dystrophy, dysferlin is likely involved in a novel pathogenic mechanism for this disease. In this study, we have analyzed the expression of dysferlin in skeletal muscle of patients with disruptions in the dystrophin-glycoprotein complex and patients with a clinical diagnosis of LGMD2B or Miyoshi myopathy. We show expression of dysferlin at the sarcolemma in normal muscle and reduced sarcolemmal expression along with accumulation of intracellular staining in dystrophic muscle. Electron microscopy in Miyoshi myopathy biopsies suggests that the cytoplasmic staining could be a result of the abundance of intracellular vesicles. Our results indicate that dysferlin expression is perturbed in LGMD and that both mutations in the dysferlin gene and disruption of the dystrophin-glycoprotein complex can lead to the accumulation of dysferlin within the cytoplasm.
最近，dysferlin被鉴定为一种与2B型肢带型肌营养不良症（LGMD2B）及其等位疾病——宫下肌病相关的新基因。dysferlin的预测结构表明它是一种可能参与膜融合的跨膜蛋白。因此，与之前在肌营养不良症中鉴定出的结构蛋白不同，dysferlin可能参与了该疾病的一种新的致病机制。在本研究中，我们分析了肌营养不良蛋白-糖蛋白复合物受损患者以及临床诊断为LGMD2B或宫下肌病患者骨骼肌中dysferlin的表达情况。我们发现，在正常肌肉中，dysferlin在肌膜上表达，而在营养不良性肌肉中，肌膜表达减少，同时细胞内染色积聚。宫下肌病活检组织的电子显微镜检查表明，细胞质染色可能是细胞内囊泡丰富的结果。我们的结果表明，dysferlin在LGMD中的表达受到干扰，dysferlin基因的突变和肌营养不良蛋白-糖蛋白复合物的破坏均可导致dysferlin在细胞质内积聚。
