摘要：
研究背景 DMD 基因点突变，主要是无义突变，可以引起基因编码提前终止，使产生的目的蛋白不稳定而降解，导致临床症状较重的Duchenne 型肌营养不良症，而在实际工作中可见临床表型为症状较轻的Becker 型肌营养不良症的DMD 点突变患者。本研究旨在探讨DMD 基因点突变导致Becker 型肌营养不良症的发病机制，以加深对Becker 型肌营养不良症基因突变类型的认识。方法 共11 例临床和肌肉活检明确诊断、多重连接依赖性探针扩增（MLPA）显示DMD 基因外显子非缺失或重复突变的Becker 型肌营养不良症患者，高通量第2 代DNA 测序法检测DMD 基因外显子突变类型。结果 11 例Becker 型肌营养不良症患者携带10 种突变类型，无突变热点；6 例携带无义突变［c.5002G>T，p.（Glu1668X）；c.1615C>T，p（. Arg539X）；c.7105G>T，p（. Glu2369X）；c.5287C>T，p（. Arg1763X）；c.9284T>G，p.（Leu3095X）］；1 例携带错义突变［c.5234G>A，p.（Arg1745His）］；2 例携带框移突变（c.10231dupT，c.10491delC）；2 例携带剪切位点突变（c.4518+3A > T，c.649 + 2T > C）。结论 DMD 基因点突变可以引起临床症状较轻的Becker 型肌营养不良症，当MLPA 技术显示DMD 基因为非缺失和重复突变时，切勿漏诊Becker型肌营养不良症，研究其发生机制对基因治疗Duchenne型肌营养不良症有重要借鉴意义。
关键词:
肌营养不良, 杜氏,
肌营养不良蛋白,
点突变
Abstract:
Background DMD gene point mutation, mainly nonsense mutation, always cause the most severe Duchenne muscular dystrophy (DMD). However, we also observed some cases of Becker muscular dystrophy (BMD) carrying DMD point mutation. This paper aims to explore the mechanism of DMD point mutation causing BMD, in order to enhance the understanding of mutation types of BMD. Methods Sequence analysis was performed in 11 cases of BMD confirmed by typical clinical manifestations and muscle biopsy. The exon of DMD gene was detected non-deletion or duplication by multiplex ligation-dependent probe amplification (MLPA). Results Eleven patients carried 10 mutation types without mutational hotspot. Six patients carried nonsense mutations [c.5002G>T, p.(Glu1668X); c.1615C > T, p.(Arg539X); c.7105G > T, p.(Glu2369X); c.5287C > T, p.(Arg1763X); c.9284T > G, p.(Leu3095X)]. One patient carried missense mutation [c.5234G > A, p.(Arg1745His)]. Two patients carried frameshift mutations (c.10231dupT, c.10491delC). Two patients carried splicing site mutations (c.4518 + 3A > T, c.649 + 2T > C). Conclusions DMD gene point mutation may result in BMD with mild clinical symptoms. When clinical manifestations suggest the possibility of BMD and MLPA reveals non?deletion or duplication mutation of DMD gene, BMD should be considered. Study on the mechanism of DMD point mutation causing BMD is very important for gene therapy of DMD.
Key words:
Muscular dystrophy, Duchenne,
Dystrophin,
Point mutation
操基清, 杨娟, 李亚勤, 冯善伟, 陈菲, 郑卉, 梁颖茵, 赵保健, 张旭, 张惠丽, 朱瑜龄, 张成. DMD 基因点突变致Becker型肌营养不良症临床研究[J]. 中国现代神经疾病杂志, 2015, 15(6): 442-447.
CAO Ji-qing, YANG Juan, LI Ya-qin, FENG Shan-wei, CHEN Fei, ZHENG Hui, LIANG Ying-yin, ZHAO Bao-jian, ZHANG Xu, ZHANG Hui-li, ZHU Yu-ling, ZHANG Cheng. Clinical study of DMD gene point mutation causing Becker muscular dystrophy[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2015, 15(6): 442-447.