慢性进行性眼外肌麻痹的分子遗传学研究

【作者】 滕蕾；

【导师】 王培林； 王修海；

【作者基本信息】 青岛大学 ， 遗传学， 2001， 硕士

【摘要】 目的 通过对慢性进行性眼外肌麻痹（CPEO，包括KSS）患者眼外肌的线粒体DNA（mtDNA）的分子遗传学研究，探讨CPEO发病的分子机制，为CPEO的诊断、治疗提供分子遗传学的理论基础和依据。方法 应用聚合酶链反应（PCR）、PCR结合限制性片段长度多态性（PCR-RFLP）技术以及PCR结合单链构象多态性（PCR-SSCP）技术，对4例CPEO患者、10例非CPEO患者的外周血单个核细胞（PBMC）、受累眼外肌（包括提上睑肌在内的7条肌肉）mtDNA的8483～13459碱基部位的缺失突变、tRNA（Leu）基因3243位点的点突变以及tRNA（Leu）基因其它位点的突变情况进行检测分析。结果 ①在1例CPEO患者眼外肌标本（提上睑肌）中检测到mtDNA的8483～13459碱基部位的缺失突变，而在其PBMC中未检测到；②在所有CPEO患者及非CPEO患者的受累眼外肌和PBMC标本中未检测出A3243G点突变；③所有标本中均未检测到tRNA（Leu）基因的其它点突变。结论 ①mtDNA的8483～13459碱基部位缺失突变与CPEO的发病有关；②在患者的受累眼外肌中检测到此缺失突变，而在其外周血中未检测到；③在CPEO患者中未检测到导致线粒体脑肌病伴高乳酸 慢性进行性眼外肌麻痹的分子遗传学研究 血症和卒中样发作（MELAS）的mtDNA 特异性突变 A3243G。④未发现CPEO患者的 mtDNA tRNA（Leu） 基因的其它点突变。更多还原

【Abstract】 Objective To study mitochondrial DNA(mtDNA) mutations in chronic progressive external ophthalmoplegia(CPEO), and explore the genetic pathogenesis of the disease. Methods The mtDNA deletion mutation, tRNA(Leu) gene A3243G point mutation and other point mutations in tRNA(Leu) gene in the peripheral blood mononuclear cells (PBMC) and the affected extra-ocular muscles (7 muscles including levator muscle of upper eyelid) of 4 CPEO patients and 10 ocular diseases (except CPEO) patients were detected by polymerase chain reaction(PCR), PCR combined with restricted fragment length polymorphism(PCR-RFLP) and PCR combined single strand conformation polymorphism(PCR-SSCP) respectively. Results ?The mtDNA deletion mutation was found in one CPEO patient抯 affected extra-ocular muscle (levator muscle of upper eyelid), but not in his PBMC; @~The tRNA(Leu) gene A3243G point mutation was not found in all the patients with or without CPEO; ?Other point mutations in tRNA(Leu) gene were not found. Conclusions ?The deletion mutation of mitochondrial DNA is related to the pathogenesis of -3- CPEO; ~ The deletion mutation can occur in affected extra-ocular muscles, but not in PBMC in the same patient ; ?The specific mutation ?tRNA(Leu) gene A3243G of mitochondrial encephalomyopathies with lactic and stroke-like episodes(MELAS ) is not found; ?Other point mutations in tRNA(Leu) gene are not found.更多还原