Larsson N G, Andersen O, Holme E, Oldfors A, Wahlström J
Department of Clinical Chemistry, Gothenburg University, Sahlgren's Hospital, Sweden.
Ann Neurol. 1991 Nov;30(5):701-8. doi: 10.1002/ana.410300511.
We investigated a family with Leber's hereditary optic neuropathy in which affected individuals were homoplasmic for the point mutation of the NADH-dehydrogenase 4 gene of mitochondrial DNA, described by Wallace and colleagues in 1988. The proband had bilateral optic atrophy, tremor, dystonia, and sharply defined lesions in the putamen on magnetic resonance images. Optic atrophy was found in another 3 of 13 investigated relatives on the maternal side. Additional neurological signs were found but only in patients with optic neuropathy. The morphological appearance and the respiratory chain function of muscle tissue were investigated in the proband, his mother, and 3 siblings. Polarographic measurements revealed complex I deficiency in the 5 investigated subjects. Morphological changes of mitochondria were found in 4 of these subjects. There was no decrease in complex I activity measured as NADH ferricyanide reductase or rotenone-sensitive NADH cytochrome c reductase activities. In other cases with complex I deficiency, good agreement between polarographic and spectrophotometric measurements was found. This study showed that there is decreased activity of complex I of the respiratory chain in muscle and that cerebral striatal lesions occur in Leber's hereditary optic neuropathy with the NADH-dehydrogenase 4 gene point mutation.
我们对一个患有Leber遗传性视神经病变的家族进行了研究，该家族中受影响个体的线粒体DNA的NADH脱氢酶4基因存在点突变，此突变由华莱士及其同事于1988年描述。先证者患有双侧视神经萎缩、震颤、肌张力障碍，磁共振成像显示壳核有边界清晰的病变。在13名接受调查的母系亲属中，另外3人也发现了视神经萎缩。还发现了其他神经系统体征，但仅见于患有视神经病变的患者。对先证者、其母亲和3名兄弟姐妹的肌肉组织的形态外观和呼吸链功能进行了研究。极谱测量显示，5名受调查对象存在复合体I缺陷。其中4名对象发现线粒体有形态学改变。以NADH铁氰化物还原酶或鱼藤酮敏感的NADH细胞色素c还原酶活性来衡量，复合体I活性并未降低。在其他存在复合体I缺陷的病例中，极谱测量和分光光度测量结果吻合良好。这项研究表明，肌肉中呼吸链复合体I的活性降低，并且在伴有NADH脱氢酶4基因点突变的Leber遗传性视神经病变中会出现脑纹状体病变。
