假肥大型肌营养不良症的基因型与临床表型关系分析

Correlation between genotypes and phenotypes in pseudohypertrophic muscular dystrophy

目的分析中国人群假肥大型肌营养不良症基因型和临床表型之间的关系。方法临床诊断Duchenne型肌营养不良症（Duchenne muscular dystrophy，DMD）和Becker型肌营养不良症（Becker muscular dystrophy，BMD）患者，应用多重探针连接依赖性扩增技术进行DMD基因检测，将基因检测结果与临床诊断比较进行统计分析。结果280例DMD基因缺失或重复患者中，DMD患者238例（85．0％），BMD患者35例（12．5％），中间型患者7例（2．5％）。DMD或BMD符合阅读框原则的有252例，占92．31％（252／273），不符合阅读框的有21例，占7．69％（21／273）。DMD基因为整码突变而患者表现为DMD的有12例（12／273，4．40％），移码突变而患者表现为BMD的有9例（9／273，3．30％）。7例中间型患者均为移码突变。结论阅读框假说可以解释大约90％DMD或BMD基因型与表现型关系，部分移码突变患者表型为BMD可有助于了解该病的发病机制，为未来治疗提供理论依据。

Objective To explore the correlation between genotypes and phenotypes in Chinese patients with pseudohypertrophic muscular dystrophy. Methods Patients with Duchenne muscular dystrophy （DMD） and Becker muscular dystrophy （BMD） were diagnosed clinically. Multiplex ligation- dependent probe amplification （MLPA） were performed to detect potential DMD gene mutations. The results were analyzed statistically. Result Among 280 patients, 238 （85.0%） were diagnosed with DMD, 35 （12. 50%） were diagnosed with BMD and 7 （2. 5%） were diagnosed with intermediate muscular dystrophin （IMD）. Among these, 252 （92.31%） were in-frame mutations, and 21 （7.69%） were out-of- frame mutations. Twelve patients with DMD have carried in-frame mutations, 9 with BMD have carried frame-shift mutations, and 7 IMD patients have carried frame-shift mutation. Conclusion Most of the genotypes and phenotypes of DMD have complied with the reading-frame hypothesis. Patients with BMD with frame-shift mutations may facilitate understanding of the pathogenesis of DMD, and provide a theoretical basis for clinical therapy.