Holt I J, Harding A E, Cooper J M, Schapira A H, Toscano A, Clark J B, Morgan-Hughes J A
University Department of Clinical Neurology, Institute of Neurology, Queen Square, London, UK.
Ann Neurol. 1989 Dec;26(6):699-708. doi: 10.1002/ana.410260603.
Analysis of mitochondrial DNA (mtDNA) in muscle and blood from 72 patients with mitochondrial myopathy showed that 30 had major deletions of a variable proportion of muscle mtDNA. All of these 30 patients presented with progressive external ophthalmoplegia and limb weakness, and 8 had the additional features of the Kearns-Sayre syndrome. Of the 42 patients without detectable muscle mtDNA deletions, 10 had progressive external ophthalmoplegia and limb weakness, 2 had the Kearns-Sayre syndrome, 11 had limb weakness without extraocular involvement, and 19 had multisystem disorders predominantly affecting the central nervous system. Only 2 patients with mtDNA deletions had clinically affected relatives, compared with 10 of those without deletions. In the 4 patients with polarographic defects exclusively involving complex I (NADH coenzyme Q reductase), the deleted protein-coding genes were confined to those for complex I subunits. Thirteen other patients with apparently identical deletions had variable clinical and biochemical features. Immunoblots of complex I polypeptides from patients with deletions were either indistinguishable from controls or showed only a mild generalized decrease in all identifiable subunits.
对72例线粒体肌病患者的肌肉和血液中的线粒体DNA（mtDNA）进行分析发现，30例患者的肌肉mtDNA有不同比例的大片段缺失。这30例患者均表现为进行性眼外肌麻痹和肢体无力，其中8例还具有凯-塞尔综合征的其他特征。在42例未检测到肌肉mtDNA缺失的患者中，10例有进行性眼外肌麻痹和肢体无力，2例有凯-塞尔综合征，11例有肢体无力但无眼外肌受累，19例有多系统疾病，主要影响中枢神经系统。与未发生缺失的患者中的10例相比，只有2例发生mtDNA缺失的患者有临床受累亲属。在仅涉及复合体I（NADH辅酶Q还原酶）的极谱缺陷的4例患者中，缺失的蛋白质编码基因仅限于复合体I亚基的基因。另外13例有明显相同缺失的患者有不同的临床和生化特征。来自发生缺失患者的复合体I多肽的免疫印迹与对照无差异，或仅显示所有可识别亚基有轻度普遍减少。
