肢带型肌营养不良和Miyoshi肌病dysferlin表达分析  

Dysferlin expression in limb-girdle muscular dystrophy and Miyoshi myopathy:analysis of 45 cases

作　　者：任守臣[1] 焉传祝[1] 李茂绪 刘淑萍[1] 吴金玲[1] 赵玉英[1] 李伟[1] 李大年[1] 

机构地区：[1]山东大学齐鲁医院神经内科,济南250012 [2]日照市中医院神经内科

出　　处：《中华医学杂志》2007年第21期1486-1490,共5页National Medical Journal of China

摘　　要：目的探讨 dysferlinopathy 的临床、病理及分子病理特征。方法对45例临床病理诊断为肢带型肌营养不良(LGMD)和 Miyoshi 肌病(MM)患者的冰冻肌肉标本通过免疫组化染色(IHC)观察 dysfedin、α-肌聚糖和肌营养不良蛋白(dystrophin)的表达,进一步用 Western 印迹分析法(WB)测定肌肉组织中 dysfedin 含量。结果在39例 LGMD 和6例 MM 患者肌肉标本中发现5例dysferlin 完全缺失,另有3例 dysferlin 表达量在正常对照值的15%以下,这8例患者符合dysferlinopathy 的诊断,其中 LGMD 3例,MM 5例。平均发病年龄为18.8岁,2例 LGMD 患者为同胞兄妹,1例 MM 患者的父母为姑表兄妹,提示本病属常染色体隐性遗传方式。血清 CK585～21 280IU/L,平均6240 IU/L,肌电图均显示肌源性损害,肌肉病理为典型肌营养不良改变,3例有炎细胞浸润。结论 dysferlinopathy 临床和普通肌肉病理缺乏特异性,部分患者肌组织中伴有炎细胞浸润,容易误诊为炎症性肌病。应用免疫组化和蛋白印迹方法对 dysferlin 的表达进行分析是诊断本病以及与炎症性肌病鉴别的必要手段。Objective To clarify the expression patterns of dysferlin in limb-girdle muscular dystrophy （LGMD） and Miyoshi myopathy （MM）, and to investigate the frequency and clinicopathologic features of dysferlinopathy. Methods The expressing patterns of dysferlin were analyzed by immunohistochemistry, with a set of antibodies against dystrophin, α-sarcoglycan and dysferlin, in the biopsied muscle specimens from 45 patients with LGMD or MM diagnosed on the basis of clinical manifestations and muscle pathological features. The specimens with abnormal dysferlin expression shown by IHC were further analyzed with Western blotting for a quantitative evaluation. Results Eight patients were proved to be primary dysferlinopathy according to total dysferlin deficiency or a significant decrease of dysferlin （less than 15% that of normal value）. The clinical manifestations of 5 of the 8 dysferlinopathy patients were consistent with those of typical MM, and the other 3 were diagnosed as with LGMD. All patients had an average onset at the age of 18.8 years. Two of them had family history, and one patient had consanguineous mating parents, meaning an autosomal recessive inheritance pattern. The serum CK levels were 6240 IU/L on average. EMG showed myogenic patterns in all patients. Muscular pathology showed typical changes of muscular dystrophy in all patients. Focal or scattered inflammatory cellular infiltrations were found in 3 cases. Conclusion The clinical and pathological features of dysferlinopathy are nonspecific. Inflammatory cellular infiltrations are relatively common in biopsied muscles of dysferlinopathy patients, which may cause misdiagnosis of inflammatory myopathy. Identification of dysferlin expression by IHC and Western blotting are essential for the diagnosis of dysferlinopathy and differential diagnosis of inflammatory myopathy.

关 键 词：肢带型肌营养不良2B型 MIYOSHI肌病 dysferlin蛋白 Westem印迹 

分 类 号：R746[医药卫生—神经病学与精神病学]