Dystrophin levels and clinical severity in Becker muscular dystrophy patients
Dystrophin levels and clinical severity in Becker muscular dystrophy patients
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DOI：
10.1136/jnnp-2013-306350
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发表时间：
2014-07-01
影响因子：
11
通讯作者：
Verschuuren, J. J.
中科院分区：
文献类型：
--
作者：
van den Bergen, J. C.;Wokke, B. H.;Verschuuren, J. J.
目的 贝克尔肌营养不良症 (BMD) 的特点是临床变异广泛。正在进行的研究探索杜氏肌营养不良症中肌营养不良蛋白的恢复，要求更好地了解肌营养不良蛋白水平与疾病严重程度之间的关系。我们在具有不同突变的 BMD 患者中研究了这种关系，其中包括一大批具有外显子 45-47 缺失的患者。方法 通过蛋白质印迹分析对胫骨前肌的新鲜肌肉活检中的肌营养不良蛋白进行定量。使用定量肌肉力量测量和功能障碍评分来评估疾病严重程度。在一个亚组中进行腿部 MRI 以检测脂肪浸润。结果 33 名 BMD 患者参与。在整个组和外显子 45-47 缺失患者的亚组中，肌营养不良蛋白水平（范围 3%-78%）与不同疾病里程碑的肌力或年龄之间没有发现线性关系。然而，肌营养不良蛋白低于10%的患者均表现出严重的病程。对整个群体进行分析时，未发现疾病严重程度与年龄之间存在相关性。相比之下，在外显子 45-47 缺失亚组中，肌肉力量和脂肪浸润水平与患者年龄显着相关。结论我们的研究表明，只要抗肌营养不良蛋白水平高于约 10%，则抗肌营养不良蛋白水平似乎不是 BMD 疾病严重程度的主要决定因素。仅在外显子 45-47 缺失亚组中发现年龄与病程之间存在显着相关性。这表明，在较高的抗肌营养不良蛋白水平下，病程更多地取决于突变位点，而不是抗肌营养不良蛋白产生的数量。
Objective Becker muscular dystrophy (BMD) is characterised by broad clinical variability. Ongoing studies exploring dystrophin restoration in Duchenne muscular dystrophy ask for better understanding of the relation between dystrophin levels and disease severity. We studied this relation in BMD patients with varying mutations, including a large subset with an exon 45-47 deletion.Methods Dystrophin was quantified by western blot analyses in a fresh muscle biopsy of the anterior tibial muscle. Disease severity was assessed using quantitative muscle strength measurements and functional disability scoring. MRI of the leg was performed in a subgroup to detect fatty infiltration.Results 33 BMD patients participated. No linear relation was found between dystrophin levels (range 3%-78%) and muscle strength or age at different disease milestones, in both the whole group and the subgroup of exon 45-47 deleted patients. However, patients with less than 10% dystrophin all showed a severe disease course. No relation was found between disease severity and age when analysing the whole group. By contrast, in the exon 45-47 deleted subgroup, muscle strength and levels of fatty infiltration were significantly correlated with patients' age.Conclusions Our study shows that dystrophin levels appear not to be a major determinant of disease severity in BMD, as long as it is above approximately 10%. A significant relation between age and disease course was only found in the exon 45-47 deletion subgroup. This suggests that at higher dystrophin levels, the disease course depends more on the mutation site than on the amount of the dystrophin protein produced.