Moraes C T, Ciacci F, Bonilla E, Ionasescu V, Schon E A, DiMauro S
Department of Genetic, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
Nat Genet. 1993 Jul;4(3):284-8. doi: 10.1038/ng0793-284.
We have identified an unusual mitochondrial (mt) tRNA mutation in a seven year-old girl with a pure myopathy. This G to A transition at mtDNA position 15990 changed the anticodon normally found in proline tRNAs (UGG) to the one found in serine tRNAs (UGA), and is the first pathogenic anticodon alteration described in a higher eukaryote. The mutant mtDNA was heteroplasmic (85% mutant) in muscle but was undetectable in white blood cells from the patient and her mother. Analysis of single muscle fibres indicated that mutant mtDNAs severely impaired mitochondrial protein synthesis and respiratory chain activity, but only when present at greater than 90%. The recessive behaviour of this mtDNA alteration may explain the patient's relatively mild clinical phenotype.
我们在一名患有单纯性肌病的7岁女童中发现了一种罕见的线粒体（mt）tRNA突变。线粒体DNA位置15990处的这种G到A的转换，将脯氨酸tRNA中正常的反密码子（UGG）变成了丝氨酸tRNA中的反密码子（UGA），这是在高等真核生物中描述的首个致病性反密码子改变。突变的线粒体DNA在肌肉中是异质性的（85%为突变型），但在患者及其母亲的白细胞中未检测到。对单根肌纤维的分析表明，突变的线粒体DNA严重损害线粒体蛋白质合成和呼吸链活性，但只有当突变型线粒体DNA的比例大于90%时才会如此。这种线粒体DNA改变的隐性特征可能解释了患者相对较轻的临床表型。
