Cytochrome c oxidase subunit I microdeletion in a patient with motor neuron disease
Cytochrome c oxidase subunit I microdeletion in a patient with motor neuron disease
复制标题
DOI：
10.1002/ana.410430119
复制
发表时间：
1998-01-01
影响因子：
11.2
通讯作者：
Scarlato, G
中科院分区：
文献类型：
--
作者：
Comi, GP;Bordoni, A;Scarlato, G
在对一名运动神经元样变性患者的严重分离性肌肉COX缺乏的研究中，发现了线粒体dna编码的细胞色素c氧化酶（COX）亚基I的框架外突变。该突变是位于COI基因5'端的异质5 bp微缺失，导致相应的翻译产物过早终止。Western blot分析、免疫组织化学和单纤维聚合酶链反应显示COX缺陷、COX I表达和突变百分比之间密切相关。COX亚基II、III和IV也减少，提示COX全酶组装有缺陷。突变Nas与线粒体疾病的临床表型异常相关，线粒体疾病是一种孤立的运动神经元疾病（MND），具有一些不典型的表现，包括早期发病，优先累及上运动神经元，脑脊液蛋白含量增加。MND可能是由氧化磷酸化（OXPHOS）的副产物自由基清除能力受损和过量产生引起的。我们的观察表明，OXPHOS损伤可能在一些MND病例的发病机制中起作用。
An out-of-frame mutation of the mitochondrial DNA-encoded subunit I of cytochrome c oxidase (COX) was discovered during investigation of a severe isolated muscle COX deficiency in a patient with motor neuron-like degeneration. The mutation is a heteroplasmic 5-bp microdeletion located in the 5' end of the COI gene, leading to premature termination of the corresponding translation product. Western blot analysis, immunohistochemistry, and single-fiber polymerase chain reaction demonstrated a tight correlation between COX defect, COX I expression, and percentage of mutation. COX subunits II, III, and IV were decreased as well, suggesting a defective assembly of COX holoenzyme. The mutation Nas associated with a clinical phenotype unusual for a mitochondrial disorder, that is, an isolated motor neuron disease (MND) with some atypical findings, including early onset, preferential involvement of the upper motor neuron, and increased cerebrospinal fluid protein content. MND may arise from impaired scavenging and overproduction of free oxygen radicals, a by-product of oxidative phosphorylation (OXPHOS). Our observation suggests that OXPHOS impairment could play a role in the pathogenesis of some MND cases.