Goto Y, Koga Y, Horai S, Nonaka I
Division of Ultrastructural Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (N.C.N.P.), Tokyo, Japan.
J Neurol Sci. 1990 Dec;100(1-2):63-9. doi: 10.1016/0022-510x(90)90014-e.
Deleted mitochondrial DNA (mtDNA) has been shown to coexist with normal mtDNA (heteroplasmy) in muscles from chronic progressive external ophthalmoplegia, including Kearns-Sayre syndrome. In this study, we correlated heteroplasmic mtDNA abnormality with clinical, biochemical and histological findings with the following results: (1) large deletions ranging from 1.8 to 8.8 kb in 22 muscle specimens from 28 patients who had ophthalmoplegia clinically and focal cytochrome c oxidase (CCO) deficiency by histochemistry, (2) no difference in clinical and biochemical findings between patients with and without mtDNA deletions, (3) no relationship between the size, site or populations of deleted mtDNA and respiratory chain enzyme activities in muscles, (4) positive correlation between the number of CCO-deficient fibers and the populations of deleted mtDNA, and (5) higher incidence of CCO-negative fibers in patients with deleted mtDNA than in those with no deletion of mtDNA. These results suggest that deleted mtDNA is, at least in part, responsible for focal CCO deficiency as a phenotypic expression and that the investigation on pathogenetic mechanism of focal CCO deficiency may provide a clue to understanding the underlying pathophysiology in this disorder.
在包括卡恩斯-塞尔综合征在内的慢性进行性眼外肌麻痹患者的肌肉中，已证实缺失的线粒体DNA（mtDNA）与正常mtDNA共存（异质性）。在本研究中，我们将异质性mtDNA异常与临床、生化和组织学结果进行关联，结果如下：（1）在28例临床上有眼外肌麻痹且通过组织化学显示局灶性细胞色素c氧化酶（CCO）缺乏的患者的22份肌肉标本中，发现了1.8至8.8 kb的大片段缺失；（2）有和没有mtDNA缺失的患者在临床和生化结果上没有差异；（3）缺失的mtDNA的大小、位置或数量与肌肉中的呼吸链酶活性之间没有关系；（4）CCO缺乏纤维的数量与缺失的mtDNA数量呈正相关；（5）与没有mtDNA缺失的患者相比，有mtDNA缺失的患者中CCO阴性纤维的发生率更高。这些结果表明，缺失的mtDNA至少部分地导致了作为表型表达的局灶性CCO缺乏，并且对局灶性CCO缺乏发病机制的研究可能为理解该疾病的潜在病理生理学提供线索。
