Chalmers R M, Lamont P J, Nelson I, Ellison D W, Thomas N H, Harding A E, Hammans S R
Neurogenetics Section, University Department of Clinical Neurology, Queen Square, London, UK.
Neurology. 1997 Aug;49(2):589-92. doi: 10.1212/wnl.49.2.589.
Subacute necrotizing encephalomyelopathy (Leigh syndrome) is associated with a number of mitochondrial DNA (mtDNA) abnormalities. We studied a family with maternally inherited encephalomyelopathy. Two siblings developed adult-onset Leigh syndrome. Muscle biopsy specimens showed enhanced succinic dehydrogenase activity and cytochrome oxidase-negative fibers. We sequenced the ATPase- and transfer RNA (tRNA)-encoding genes of mtDNA and identified a novel mtDNA valine tRNA mutation at base pair 1644. This transversion was heteroplasmic in blood and muscle in all individuals studied, and the proportion of mutant mtDNA correlated with disease severity. This is the first heteroplasmic transversion within a mtDNA tRNA gene and the second pathogenic mtDNA tRNA(Val) mutation to be associated with human disease.
亚急性坏死性脑脊髓病（Leigh综合征）与多种线粒体DNA（mtDNA）异常有关。我们研究了一个患有母系遗传脑脊髓病的家系。两名同胞患成年期发病的Leigh综合征。肌肉活检标本显示琥珀酸脱氢酶活性增强以及细胞色素氧化酶阴性纤维。我们对mtDNA的ATP酶和转运RNA（tRNA）编码基因进行了测序，并在碱基对1644处鉴定出一种新的mtDNA缬氨酸tRNA突变。这种颠换在所有研究个体的血液和肌肉中均为异质性，并且突变mtDNA的比例与疾病严重程度相关。这是mtDNA tRNA基因内的首个异质性颠换，也是与人类疾病相关的第二个致病性mtDNA tRNA（Val）突变。
