用基因缺陷、蛋白质空间结构改变浅析Duchenne型肌营养不良症发病机制

目的：研究dystrophin基因缺陷、蛋白疏水性改变和空间结构改变与临床表型的关系，从分子水平探索Duchenne型肌营养不良症（DMD）发病机制。方法:分析59例缺失型突变的DMD/BMD患者基因检测结果，以信息生物学方法分析dystrophin蛋白疏水性和三维结构改变与临床表型的关系。结果:50例移码突变均为DMD。累及第3疏水峰的5例整码突变4例为DMD，1例BMD。3号外显子缺失后dystrophin的氨基端空间位置发生扭转，影响dystrophin与肌钙蛋白结合而致病。结论:肌营养不良的临床表型轻重与缺失是否破坏阅读框、累及第3疏水峰以及蛋白空间结构改变有关。

Mechanism of DMD with gene defect and change of protein structure

AIM: To examine the relationship between the gene defect, change of protein hydrophobicity, spacial structure change and clinical phenotypes of Duchenne muscular dystrophy（DMD）,and to explore the molecular pathogenesis of DMD. METHODS: The gene sequences of 59 cases of DMD/BMD patients with deletion from mutation were analyzed. The relationship between the protein hydrophobicity, 3D-spacial structure and clinical phenotypes was examined by biological informatic technology. RESULTS: 50 cases of frameshift mutation were all DMD. In other 5 cases with codon mutation that involved the 3rd hydrophobic region, 4 cases were diagnosed as DMD and the rest one was BMD. The exon 3 deletion leaded to the intortion of dystrophin N-terminal, which in turn affected the combination of dystrophin and troponin resulting in the DMD pathopoiesis. CONCLUSION: The severity of clinical phenotypes of muscular dystrophy diseases is related to whether the deletion destroys the reading frame, involves the 3rd hydrophobic region or changes the protein special structure. The biological informatic technology provides a new potential research methodology for studying the pathogenesis of DMD.