Nicholson L V, Johnson M A, Gardner-Medwin D, Bhattacharya S, Harris J B
Muscular Dystrophy Group Research Laboratories, Newcastle General Hospital, Newcastle-upon-Tyne, Great Britain.
Acta Neuropathol. 1990;80(3):239-50. doi: 10.1007/BF00294640.
This report documents the results of an integrated biochemical and immunocytochemical investigation into the expression of dystrophin (the protein product of the Duchenne muscular dystrophy gene) in muscle biopsies from 226 patients. It is the first study in which dystrophin has been analysed on blots and on tissue sections in such a large number of patients using the same (monoclonal) antibody. The 140 patients with Xp21 muscular dystrophy who were included in this study represent a continuous spectrum of disease severity and this range was reflected in the heterogeneity of dystrophin expression which was observed with respect to abundance, size and the pattern of tissue localisation. Approximately 40% of biopsies obtained from patients diagnosed as having Duchenne muscular dystrophy (DMD) contained isolated clearly positive fibres and a further 20% had very weak labelling on a large number of fibres. Biopsies from patients with Becker muscular dystrophy (BMD) showed labelling patterns which varied from weak labelling on the majority of fibres to clear labelling on all fibres. Typically, however, there was inter- and intra-fibre variation in labelling intensity. Approximately 85% of the 52 BMD and 54 DMD patients who had unequivocal labelling on blots demonstrated a protein of abnormal size. The remaining 15% had a protein of normal size but reduced abundance. Overall, the estimated abundance of dystrophin correlated well with clinical assessments of the disease severity expressed in patients. We conclude that dystrophin analysis is an essential and dependable technique for the differential diagnosis of patients with Xp21 muscular dystrophy.
本报告记录了对226例患者肌肉活检样本中肌营养不良蛋白（杜兴氏肌营养不良症基因的蛋白质产物）表达情况进行的综合生化及免疫细胞化学研究结果。这是首次使用相同（单克隆）抗体，对如此大量患者的印迹和组织切片进行肌营养不良蛋白分析的研究。本研究纳入的140例Xp21型肌营养不良症患者代表了疾病严重程度的连续谱系，这种范围反映在肌营养不良蛋白表达的异质性上，在丰度、大小和组织定位模式方面均有观察到。从被诊断为杜兴氏肌营养不良症（DMD）的患者获取的活检样本中，约40%含有孤立的明显阳性纤维，另有20%在大量纤维上有非常微弱的标记。贝克氏肌营养不良症（BMD）患者的活检样本显示出标记模式的差异，从大多数纤维上的微弱标记到所有纤维上的清晰标记。然而，典型的情况是，纤维间和纤维内的标记强度存在差异。在印迹上有明确标记的52例BMD患者和54例DMD患者中，约85%显示出大小异常的蛋白质。其余15%的蛋白质大小正常但丰度降低。总体而言，估计的肌营养不良蛋白丰度与患者疾病严重程度的临床评估结果密切相关。我们得出结论，肌营养不良蛋白分析是诊断Xp21型肌营养不良症患者的一项重要且可靠的技术。
