Morgan-Hughes J A, Cooper J M, Schapira A H, Sweeny M, Holt I J, Harding A E, Clark J B
Institute of Neurology Queen Square, London, U.K.
Rev Neurol (Paris). 1991;147(6-7):450-4.
Deletions of the mitochondrial genome were identified in 21 out of 58 patients (36 percent) with mitochondrial myopathies, 47 of whom had defects in the mitochondrial respiratory chain. In cases with Complex I defects, the deleted regions of mtDNA, were confined to structural genes encoding Complex I subunits but additionally involved the intervening tRNA genes and in one case included the large and small rRNA genes. In cases with more extensive loss of respiratory chain function, the deletions eliminated genes encoding subunits of Complexes I, IV and V, as well as several tRNAs. Complex I and Complex IV polypeptides were usually normal in deleted cases. This was in contrast to 7 out of 22 patients without detectable mtDNA deletions, who showed specific deficiencies of subunits encoded by nuclear genes. Further studies in one of these cases pointed to defective translocation of the Rieske precursor from the cytosol into the mitochondria. The genetic basis of the disease in 15 cases without detectable deletions or specific subunit deficiencies, remains unknown. The multiple biochemical abnormalities encountered in these cases would be consistent with more subtle alterations of the mitochondrial genome.
在58例线粒体肌病患者中，有21例（36%）被鉴定出线粒体基因组缺失，其中47例存在线粒体呼吸链缺陷。在复合体I缺陷的病例中，线粒体DNA的缺失区域局限于编码复合体I亚基的结构基因，但还涉及到其间的tRNA基因，在1例中还包括大、小rRNA基因。在呼吸链功能丧失更广泛的病例中，缺失消除了编码复合体I、IV和V亚基的基因，以及几种tRNA。在缺失病例中，复合体I和复合体IV多肽通常是正常的。这与22例未检测到线粒体DNA缺失的患者中的7例形成对比，后者表现出核基因编码亚基的特异性缺陷。对其中1例病例的进一步研究表明，Rieske前体从胞质溶胶转运到线粒体存在缺陷。15例未检测到缺失或特异性亚基缺陷的病例中，疾病的遗传基础仍然未知。这些病例中遇到的多种生化异常与线粒体基因组更细微的改变是一致的。
