期刊
ANNALS OF NEUROLOGY
卷 68, 期 6, 页码 845-854出版社
WILEY
DOI: 10.1002/ana.22111
关键词
-
资金
- Ministry of Health, Labour, and Welfare of Japan [15B-4, 18A-5]
- Ministry of Education, Culture, Sports, Science and Technology [17790738]
- Japan Health Sciences Foundation [KHD2207]
- Grants-in-Aid for Scientific Research [17790738] Funding Source: KAKEN
Objective: To character ze the clinical features and clarify the pathogenicity of benign cytochrome c oxidase deficiency myopathy. Methods: The study included 8 patients with the phenotype of this disease. Six patients underwent muscle biopsies and all the 8 underwent mitochondrial DNA analyses. To confirm the pathogenicity of the detected mitochondrial DNA mutation, we performed northern blot analysis, using muscle specimens, and blue native polyacrylamide gel electrophoresis and respiratory chain enzyme activity assay of transmitochondrial cell lines (cybrids). Results: Clinical symptoms were limited to skeletal muscle and improved spontaneously in all cases; however, 2 siblings had basal ganglia lesions. In all patients, we identified a homoplasmic m.14674T>C or m.14674T>G mitochondrial transfer RNA-glutamate mutation. Northern blot analysis revealed decreased levels of mitochondrial transfer RNA-glutamate molecules. Muscle specimens and cybrids derived from patients showed decreased activity of respiratory complexes IV, and/or I, III; however, this was normal in naive myoblasts. Interpretation: Identification of a novel m.14674T>G mutation in addition to m.14674T>C indicated the importance of this site for disease causation. Analyses of cybrids revealed the pathogenicity of m.14674T>C mutation, which resulted in defects of cytochrome c oxidase and multiple respiratory chain enzymes. Furthermore, patients with basal ganglia lesions provided new insights into this disease, in which only skeletal muscle was thought to be affected. Normal respiratory chain enzyme activities in naive myoblasts suggested the compensatory influence of nuclear factors, which may be clue to understanding the mechanisms of spontaneous recovery and low penetrance in families carrying the mutation. ANN NEUROL 2010;68:845-854
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据