MITOCHONDRIAL-DNA DELETIONS IN PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA AND KEARNS-SAYRE SYNDROME
MITOCHONDRIAL-DNA DELETIONS IN PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA AND KEARNS-SAYRE SYNDROME
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DOI：
10.1056/nejm198905183202001
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发表时间：
1989-05-18
影响因子：
158.5
通讯作者：
ROWLAND, LP
中科院分区：
文献类型：
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作者：
MORAES, CT;DIMAURO, S;ROWLAND, LP
我们研究了骨骼肌线粒体DNA缺失与线粒体肌病临床表现的相关性，线粒体肌病是一组由线粒体生化异常或组织化学导致肌纤维红色外观的形态学变化定义的疾病。我们对123例不同线粒体肌病或脑肌病患者的肌肉线粒体DNA进行了基因组Southern印迹分析。在32例患者的线粒体DNA中发现了缺失，所有这些患者都患有进行性眼外肌麻痹。一些患者只有眼肌病变，而另一些患者有Kearns-Sayre综合征，一种以眼肌麻痹、色素性视网膜病变、心脏传导阻滞和小脑共济失调为特征的多系统疾病。这些缺失的大小范围从1.3到7.6个酶，并被定位到线粒体DNA的不同位点，但在11名患者的相同位置发现了相同的4.9个酶缺失。 生化分析表明，减少活动的NADH脱氢酶，鱼藤酮敏感的NADH-细胞色素c还原酶，琥珀酸-细胞色素c还原酶和细胞色素c氧化酶，四个酶的线粒体呼吸链含有线粒体DNA编码的亚基。我们的结论是，肌肉线粒体DNA的缺失与眼肌麻痹，并可能导致线粒体功能受损。然而，临床和生化表型与缺失之间的确切关系仍有待确定。
We investigated the correlations of deletions of mitochondrial DNA in skeletal muscle with clinical manifestations of mitochondrial myopathies, a group of disorders defined either by biochemical abnormalities of mitochondria or by morphologic changes causing a ragged red appearance of the muscle fibers histochemically. We performed genomic Southern blot analysis of muscle mitochondrial DNA from 123 patients with different mitochondrial myopathies or encephalomyopatheis. Deletions were found in the mitochondrial DNA of 32 patients, all of whom had progressive external ophthalmoplegia. Some patients had only ocular myopathy, whereas others had Kearns-Sayre syndrome, a multisystem disorder characterized by ophthalmoplegia, pigmentary retinopathy, heart block, and cerebellar ataxia. The deletions ranged in size from 1.3 to 7.6 kilobases and were mapped to different sites in the mitochondrial DNA, but an identical 4.9-kilobases deletion was found in the same location in 11 patients. Biochemical analysis showed decreased activities of NADH dehydrogenase, rotenone-sensitive NADH-cytochrome c reductase, succinate-cytochrome c reductase, and cytochrome c oxidase, four enzymes of the mitochondrial respiratory chain containing subunits encoded by mitochondrial DNA. We conclude that deletions of muscle mitochondrial DNA are associated with ophthalmoplegia and may result in impaired mitochondrial function. However, the precise relation between clinical and biochemical phenotypes and deletions remains to be defined.