【摘要】 为了解东北地区Duchenne/Becker型肌营养不良症患者基因缺失的分布及进行产前基因诊断 ,用 12对引物以多重PCR法检测 12 0例DMD/BMD患者 ,并分析缺失型患者dystrophin基因的断裂点分布及各引物优化组合 ,并将高危男性胎儿行缺失检测。结果表明 ,缺失检出率为 4 9 2 % ,6 6 4 %的断裂点位于内含子 4 4～ 5 2内 ,以内含子5 0为最多 (14 8% ) ,4对外显子引物的优化组合为外显子 4 8、5 1、4 5和 8,总检出率为 4 1 7% ;2 9例高危胎儿中 9例男性胎儿为缺失型 ,缺失位点与先证者相同。通过首次对我国东北地区DMD/BMD患者筛查缺失发现dystrophin基因缺失主要分布于两个热区内 ,与国内其他地区比较外显子 8附近区域可能是该地区缺失断裂的高发区 ;内含子4 4～ 5 2高度不稳定 ,其中内含子 4 4的稳定性要高于中央缺失热区的稳定性 ,内含子 5 0的不稳定性存在地区及种族差异 ;引物优化组合为检测患者及产前基因诊断提供了捷径 ,尤其是对散发家系是可行的并且有其优越性。更多还原

【Abstract】 To detect the distribution characteristics of dystrophin gene deletions of the DMD/BMD patients in the northeast of China and apply for prenatal gene diagnosis, we have analyzed the distribution of the breakpoints of the deleted-patients and the optimized primer-assembly after screening deletions of 120 DMD/BMD patients via multiplex PCR with 12-pair primers and male high-risk fetuses have been detected deletion by multiplex PCR. Results indicated the deletion frequency was 49.2%, about 66.4% deletion breakpoints positioned in introns 44～52,intron 50 was the highest breakpoint (14.8%). The optimized four-primer-assembly was the primers of exon 48, 51, 45 and 8,which could detect 41.7% deletions of all cases;9 deletions male ones of 29 high-risk fetuses were detected, who had the same deletion-segments as their probands. For the first time screening deletions of DMD/BMD patients in the northeast of China, we have found distribution of the deletions mainly lied in two hot-spots, neighboring regions of exon 8 might be a real deletion ‘hot spot’ in this area compared with other areas of our country; introns 44～52 of dystrophin gene were highly unstable and prone to break:intron 44 was more stable than the whole molecular region of ‘central deletion hot spot’ and the unstability of intron 50 changed along with the regional and ethnic difference; the optimized primer-assembly provided the short-cut for detecting patients and making prenatal gene diagnosis,especially it’s feasible and advantageous for the isolated pedigrees.更多还原