抗肌萎缩蛋白基因非缺失／重复突变引起的Becker型肌营养不良症的研究

Study of dystrophin gene non-deletion/duplication mutations causing Becker muscular dystrophy

目的探讨Becker型肌营养不良症（Becker muscular dystrophy，BMD）的基因突变类型，增加对抗肌萎缩蛋白基因非缺失／重复突变引起BMD的认识。方法收集2例BMD患者的临床资料，应用多重连接依赖式探针扩增（（multiplex ligation-dependent probe amplification assay, MLPA） ）方法对抗肌萎缩蛋白基因进行分析，并对其肌肉进行苏木素伊红（hematoxylin—eosin，HE）染色、抗肌萎缩蛋白（dystrophin）染色及电镜检测。结果2例患者经MLPA方法检测抗肌萎缩蛋白基因均呈非缺失／重复突变类型，肌肉活检光镜和电镜均呈肌营养不良改变。例1患者染色示肌膜dystrophin大部分呈不连续弱阳性，部分为阴性。例2患者染色示肌膜dystrophin-C为阴性，dystrophin—N为阳性。结论对于抗肌萎缩蛋白基因非缺失／重复突变的临床症状较轻的患者，进行肌肉活检和抗肌萎缩蛋白免疫组化将有助于明确诊断BMD及判断其预后。

Objective To identify potential mutations in patients featuring Becker muscular dystrophy （BMD） and to enhance the understanding of non-deletion/duplication mutations of the dystrophin gene causing BMD. Methods Clinical data of two patients affected with BMD were collected. Potential mutations in the dystrophin gene were screened with multiplex ligation dependent probe amplification assay （MLPA）. Biopsied muscle samples were examined with HE staining, immnostaining with anti dystrophin antibody, and electronic microscopy. Results MLPA assay suggested that both cases were probably due to non- deletion/duplication mutations of the dystrophin gene. Light and electronic microcopy of skeletal muscle biopsies confirmed dystrophic changes in both patients. For patient A, immunostaining showed noncontiguous weak staining for most parts of sarcolemma. For patient B, immunostaining showed positive result with N-terminal anti dystrophin antibody and negative result with C-terminal anti-dystrophin antibody. Conclusion For patients with mild phenotypes but without dystrophin gene deletion/duplication, muscle biopsy and immunochemistry are helpful for diagnosis and prognosis.