A POINT MUTATION IN THE MITOCHONDRIAL TRANSFER RNALEU(UUR) GENE IN MELAS (MITOCHONDRIAL MYOPATHY, ENCEPHALOPATHY, LACTIC-ACIDOSIS AND STROKE-LIKE EPISODES)
A POINT MUTATION IN THE MITOCHONDRIAL TRANSFER RNALEU(UUR) GENE IN MELAS (MITOCHONDRIAL MYOPATHY, ENCEPHALOPATHY, LACTIC-ACIDOSIS AND STROKE-LIKE EPISODES)
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DOI：
10.1016/s0006-291x(05)80860-5
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发表时间：
1990-12-31
影响因子：
3.1
通讯作者：
OHTA, S
中科院分区：
文献类型：
--
作者：
KOBAYASHI, Y;MOMOI, MY;OHTA, S
线粒体肌病、脑病、乳酸酸中毒和卒中样发作（MELAS）是一组主要的异质性线粒体疾病。为了鉴定缺陷基因，通过使用扩增的DNA片段作为测序模板对来自MELAS患者的线粒体DNA进行测序。在整个线粒体基因的16.6kbp中确定的14.1kbp中，至少有21个核苷酸与对照人线粒体DNA的核苷酸不同。其中一个替换是tRNALeu（UUR）基因中剑桥核苷酸数3243处A到G的转换。这种核苷酸不仅在许多线粒体tRNA中是保守的，而且在大多数胞质tRNA分子中也是保守的。通过该核苷酸的取代获得了阿帕I限制性位点。阿帕Ⅰ酶切结果显示，6例患者的线粒体DNA在第3,243位核苷酸处均为G，而11例对照者均为G。这一结果有力地表明，线粒体tRNALeu基因突变导致MELAS。
Mitochondrial myopathy, encephalopathy, lactic acidosis and strokelike episode (MELAS) is a major group of heterogeneous mitochondrial disorders. To identify the defective gene, mitochondrial DNA from a patient with MELAS was sequenced by using amplified DNA fragments as sequencing templates. In 14.1 kbp determined out of 16.6 kbp of the whole mitochondrial gene, at least 21 nucleotides were different from those of a control human mitochondrial DNA. One of the substitutions was a transition of A to G in the tRNALeu (UUR) gene at Cambridge nucleotide number of 3,243. This nucleotide is conserved not only in many mitochondrial tRNAs but in most cytosolic tRNA molecules. An Apa I restriction site was gained by the substitution of this nucleotide. The Apa I digestion of the amplified DNA frgment revealed that all independent 6 patients had G at nucleotide number of 3,243 in their mitochondrial DNAs, but none of 11 control individuals had G at this position. This result strongly sugests that the mutation in the mitochondrial tRNALeu gene causes MELAS.