中国西南地区170例杜氏/贝氏肌营养不良症dystrophin基因变异谱分析

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。

Gene Mutation Spectrum Analysis of 170 Patients with Duchenne/Bayesian Muscular Dystrophy inSouthwest of China

Objective To determine gene variations and genotype-phenotype correlations in Duchenne/Bayesian muscular mystrophy (DMD/BMD) patients, and the association between dystrophin gene polymorphisms and clinical phenotype. Methods Multiplex ligation-dependent probe amplification (MLPA) was adopted to detect dystrophin gene variations in 170 patients. Sanger sequencing was performed in 3 cases with decreased peaks in MLPA results. Results The MLPA detected 72.94% mutations in dystrophin gene, including 62.35% (106/170) deletions, 8.82% (15/170) duplications, and 1.76% (3/170) point mutations. 64 different types of mutations were found. 75.47% of deletions occurred in the range from exon 44 to 55. Most 5’ breakpoints of exonic variations were located in 2 hotspots (major hotspot: intron 43-55; minor hotspot: intron 1-20), which is different from findings of other studies. Genotype-phenotype analysis showed that the severity of DMD/BMD was associated with frame shift mutation ( r =0.640, P<0.001) but not with deletions or duplications. Conclusion Deletions and duplications of exon compose the main type of dystrophin gene mutations. DMD/BMD is associated with frame shift mutation.