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反义寡核苷酸干预剪接治疗Duchenne型肌营养不良 被引量：1

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摘要 　X-连锁的dystrophin基因是目前人类基因组中最大的基因,长2400kb,有79个外显子,所以易于发生重排和重组而引起突变.大部分突变为一个或多个外显子缺失（60%）,其他为重复突变（6%）、置换和点突变等.突变可破坏dystrophin基因转录的阅读框,使dystrophin蛋白的合成提前终止引起Duchenne型肌营养不良（Duchenne muscular dystrophy,DMD）.dystrophin为一杆状蛋白,相对分子质量为427 000,含有4个结构域,即N-端区、中央杆状区、半胱氨酸富集区、C-端区.中央杆状区由24个血影蛋白样重复序列和4个铰链区构成,占整个蛋白长度的80%.dystrophin蛋白把细胞骨架肌球蛋白固定到肌纤维膜,对维持细胞膜的完整性是必不可少的.dystrophin蛋白缺乏使细胞膜的脆性增加,易于受到肌肉收缩引起的机械压力的损伤.DMD的发病率约为1/3500名新生男婴,是最严重和最常见的进展性肌萎缩性疾病,患者通常于20多岁死于呼吸、循环衰竭.其中1/3的病例由新的突变引起,所以依靠遗传咨询和产前诊断不能完全消除此病,还需要一种有效的治疗方法.最近的研究显示用反义寡核苷酸（antisense oligonucleotides,AOs）干预剪接诱导外显子跳读是一种有前景的治疗方法.我们就关于干预剪接治疗DMD在动物模型和人体细胞内研究中的进展以及需要解决的主要问题作一综述.
作者 周畅 张成
机构地区 广州中山大学附属第一医院神经内科
出处 《中华神经科杂志》 CAS CSCD 北大核心 2006年第8期565-567,共3页 Chinese Journal of Neurology
关键词 DUCHENNE型肌营养不良 反义寡核苷酸 治疗方法 DYSTROPHIN蛋白 DYSTROPHIN基因 剪接 人类基因组 相对分子质量
分类号 R746.2 [医药卫生—神经病学与精神病学]
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参考文献20

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二级参考文献5

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共引文献1

同被引文献34

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引证文献1

二级引证文献7

中华神经科杂志
2006年 第8期

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