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目的构建中国西南地区杜氏/贝氏肌营养不良症(DMD/BMD)dystrophin基因变异谱,探讨dystrophin基因型与临床表型之间的关系。方法采用多重连接探针扩增技术(multiplex ligation-dependent probe amplification,MLPA)对170例DMD/BMD患者进行dystrophin基因分析,其中3例怀疑点突变患者采用Sanger测序分析基因突变位点。结果 Dystrophin基因突变MLPA检出率为72.94%,其中基因缺失、重复及点突变所占比例分别为62.35%(106/170),8.82%(15/170)及1.76%(3/170)。共发现64种不同类型突变,连续外显子44~55缺失突变型占全部缺失型患者的75.47%。大部分5′端断裂点集中在2个热区(主热区:内含子43~55;次热区:内含子1~20)。基因型-表型分析显示DMD/BMD严重程度与基因缺失型或重复型无关,而与改变开放阅读框架型突变有关(r=0.640,P<0.001)。结论连续外显子缺失或重复是dystrophin基因突变的主要类型,DMD/BMD严重程度与其改变开放阅读框架型突变有关。
Objective To construct the dystrophin gene mutation spectrum of Duchenne / Behs disease (DMD / BMD) in Southwest China and to explore the relationship between dystrophin genotype and clinical phenotype. Methods Dystrophin gene analysis was performed in 170 patients with DMD / BMD using multiplex ligation-dependent probe amplification (MLPA). Three of the suspected mutations were analyzed by Sanger sequencing. Results The detection rate of MLPA for Dystrophin gene mutation was 72.94%. The percentage of gene deletion, duplication and point mutation were 62.35% (106/170), 8.82% (15/170) and 1.76% (3/170) respectively. A total of 64 different types of mutations were found, and 44 to 55 deletion mutations of consecutive exons accounted for 75.47% of all deletion types. Most of the 5 ’end breakpoints are concentrated in two hot zones (main hot zone: intron 43-55; sub-hot zone: intron 1-20). Genotype-phenotype analysis showed that the severity of DMD / BMD was not related to gene deletion or duplication but was associated with altered open reading frame-type mutations (r = 0.640, P <0.001). Conclusions Continuous exon deletion or duplication is the main type of dystrophin gene mutation. The severity of DMD / BMD is related to the change of open reading frame mutation.