Voit T, Stuettgen P, Cremer M, Goebel H H
Department of Pediatrics, University of Düsseldorf.
Neuropediatrics. 1991 Aug;22(3):152-62. doi: 10.1055/s-2008-1071434.
Dystrophin is the gene product of the Duchenne (DMD) and Becker (BMD) muscular dystrophy gene locus on the short arm of the X chromosome. Complete lack of dystrophin is pathognomonic for DMD and variable changes of the molecule may be observed in the milder allelic form of BMD. In the present study the two methods available for dystrophin assessment, immunofluorescence detections on cryosections (IF) and Western blotting (WB) were systematically compared using polyclonal and monoclonal antibodies to various regions along the dystrophin molecule. A total of 95 patients with DMD or BMD were investigated including two female patients. Dystrophin assessment revealed abnormal abundance and/or distribution in all 95 patients with DMD or BMD. Only trace amounts of dystrophin were detected in 29% of the DMD patients and complete lack of dystrophin was found in 71%. In two females with DMD but with normal karyotype single dystrophin-positive fibres were found among more than 90% negative fibres. Out of 26 patients with BMD 19 (73%) had a dystrophin molecule of abnormal molecular weight. The results of IF were largely compatible with those from WB but differences were also observed, e.g. one barely symptomatic BMD patient with dystrophin of increased molecular weight showed normal IF. Out of four carriers of BMD three showed evidence of reduced dystrophin immunostaining in some muscle fibres. In 20 other patients limb girdle muscualar dystrophy with "Duchenne-like" or "Becker-like" phenotype was suspected because dystrophin showed normal abundance and distribution. Focal discontinuity of muscle cell-surface dystrophin staining was observed in one patient with a congenital, autosomal recessive muscular dystrophy and in one out of five patients with polymyositis/dermatomyositis. The study emphasizes the need for, and value of, dystrophin assessment in every case of suspected BMD or DMD.
肌营养不良蛋白是位于X染色体短臂上的杜兴氏（DMD）和贝克氏（BMD）肌营养不良基因位点的基因产物。完全缺乏肌营养不良蛋白是DMD的病理特征，在症状较轻的BMD等位基因形式中可能观察到该分子的变化。在本研究中，使用针对肌营养不良蛋白分子不同区域的多克隆和单克隆抗体，系统地比较了两种可用于评估肌营养不良蛋白的方法，即冷冻切片上的免疫荧光检测（IF）和蛋白质印迹法（WB）。共调查了95例DMD或BMD患者，包括两名女性患者。肌营养不良蛋白评估显示，所有95例DMD或BMD患者的肌营养不良蛋白丰度和/或分布均异常。在29%的DMD患者中仅检测到微量肌营养不良蛋白，71%的患者完全缺乏肌营养不良蛋白。在两名核型正常的DMD女性患者中，在90%以上的阴性纤维中发现了单根肌营养不良蛋白阳性纤维。在26例BMD患者中，19例（73%）的肌营养不良蛋白分子分子量异常。IF结果与WB结果基本一致，但也观察到差异，例如，一名症状轻微、肌营养不良蛋白分子量增加的BMD患者的IF结果正常。在4名BMD携带者中，有3名在某些肌纤维中显示出肌营养不良蛋白免疫染色减少的证据。在另外20例患者中怀疑为肢带型肌营养不良，具有“杜兴氏样”或“贝克氏样”表型，因为肌营养不良蛋白显示出正常的丰度和分布。在一名先天性常染色体隐性肌营养不良患者和五名多发性肌炎/皮肌炎患者中的一名患者中观察到肌细胞表面肌营养不良蛋白染色的局灶性中断。该研究强调了在每例疑似BMD或DMD病例中进行肌营养不良蛋白评估的必要性和价值。
