Mäkelä-Bengs P, Suomalainen A, Majander A, Rapola J, Kalimo H, Nuutila A, Pihko H
Department of Human Molecular Genetics, National Public Health Institute, Helsinki, Finland.
Pediatr Res. 1995 May;37(5):634-9. doi: 10.1203/00006450-199505000-00014.
We describe a four-generation family with a maternally inherited mitochondrial disorder. The symptoms were restricted to the CNS and muscle, the most common features being subacute necrotizing encephalomyopathy, cognitive impairment, ataxia, retinitis pigmentosa, infantile spasms, and optic atrophy. A point mutation at the nucleotide 8993 of the gene encoding subunit 6 of the ATP synthase, associated with the neurogenic muscle weakness, ataxia, retinitis pigmentosa (NARP) syndrome, was shown to be inherited maternally in this family, and a clear correlation was found between the clinical severity of the disease and the proportion of mutant mtDNA. Analysis of oxidative phosphorylation in mitochondria carrying 80% mutant mitochondrial DNA showed a reduction of the ATP generation rate coupled to substrate oxidation.
我们描述了一个患有母系遗传线粒体疾病的四代家族。症状局限于中枢神经系统和肌肉，最常见的特征是亚急性坏死性脑病、认知障碍、共济失调、色素性视网膜炎、婴儿痉挛和视神经萎缩。编码ATP合酶亚基6的基因核苷酸8993处的一个点突变，与神经源性肌无力、共济失调、色素性视网膜炎（NARP）综合征相关，在这个家族中显示为母系遗传，并且发现疾病的临床严重程度与突变型线粒体DNA的比例之间存在明显的相关性。对携带80%突变型线粒体DNA的线粒体中的氧化磷酸化分析表明，与底物氧化偶联的ATP生成速率降低。
