医药学论文：中国人抗肌营养不良蛋白基因缺失的分布特点[1]

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关键字：患者 国内 位于 引物 缺失 基因缺失 内含子 检出率 断裂点 外显子　　【摘要】　目的　了解国内Duchenne/Becker型肌营养不良症(DMD/BMD)患者基因缺失的分布特点。方法　用12对引物以多重PCR检测与56例DMD/BMD患者，分析缺失型患者抗肌营养不良蛋白(dystrophin)基因缺失的断裂点分布， 并结合国内文献报道的221例病例资料，分析9对引物的总检出率及各引物的最佳组合。结果　国内dystrophin基因缺失断裂点72%位于44～51号内含子内，以44号内含子最多(22%)，50号内含子次之(17%), 位于45～51号内含子内的断裂点是44号内含子的2.3倍。7号内含子断裂较少，仅4%的断裂点位于该内含子。9对引物的总检出率为48%，其中5对引物的总检出率为46%。两对引物的最佳组合为48号和17号，可检出35%的患者。结论　国内dystrophin基因44～51号内含子高度不稳定，容易发生断裂。7号内含子可能不是国内dystrophin基因缺失断裂的高发区域。在国内5对引物的总检出率接近9对引物，48号和17号外显子的二重PCR扩增对于全国范围内DMD/BMD的筛选，尤其是结合其他方法进行大范围的产前筛选，不失为一种可取的选择。

　　【Abstract】　Objective　To understand the distributional characteristics of dystrophin gene deletion in Chinese population.Methods　56 Duchenne/Becker muscular dystrophy (DMD/BMD) patients were detected by twelve primers mPCR (9 primers plus exon 7,50,52) and the distribution of the breakpoints of dystrophin gene deletion was analyzed. Combining with the 221 unrelated DMD/BMD cases reported in the published papers in China, we analyzed the positive ratio detected by the nine primers mPCR and the best primers combination to detect DMD/BMD patients.Results　About 72% of deletion breakpoints fell in intorns 44～51 in the Chinese&nbs p;DMD/BMD patients. About 22% of deletion breakpoints fell in intron 44 , 17% in intron 50, whereas the majority (50%) were located within the segments encompassing introns 45～51. Only 4% of deletion breakpoints fell in intron 7. Nine primers mPCR could detect 48% of all the cases of DMD/BMD, and five (exons 12,51,17,48,45) of these nine primes could detect 46% of all the cases of DMD/BMD. The best two-primer combination was exons 48 and 17, which could detect 35% deletion of all the DMD/BMD patients.Conclusions　 Introns 44 ～ 51 were highly unstable and prone to break. Intron 7 might not be a real deletion “hot spot” in the Chinese population. In China, the positive rate of deletion detection with five primers mPCR was almost the same as that with nine primers mPCR. Detecting deletion of exons 48 and 17医药学论文