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  

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

作　　者：王军[1] 彭武[1] 胡雪姣[1] 尚孟乔 周娟[1] 周易[1] 叶远馨[1] 宋兴勃[1] 陆小军[1] 应斌武[1] 

机构地区：[1]四川大学华西医院实验医学科,临床分子诊断实验室,成都610041

出　　处：《四川大学学报（医学版）》2016年第2期232-237,共6页Journal of Sichuan University(Medical Sciences)

基　　金：国家自然科学基金(No.81472026)资助

摘　　要：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 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 3cases 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 2hotspots（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,P0.001）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.

关 键 词：杜氏肌营养不良症 贝氏肌营养不良症 DYSTROPHIN基因 多重连接探针扩增 

分 类 号：R746.2[医药卫生—神经病学与精神病学]