A MUTATION IN THE TRANSFER RNALEU(UUR) GENE ASSOCIATED WITH THE MELAS SUBGROUP OF MITOCHONDRIAL ENCEPHALOMYOPATHIES
A MUTATION IN THE TRANSFER RNALEU(UUR) GENE ASSOCIATED WITH THE MELAS SUBGROUP OF MITOCHONDRIAL ENCEPHALOMYOPATHIES
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DOI：
10.1038/348651a0
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发表时间：
1990-12-13
期刊：
影响因子：
64.8
通讯作者：
HORAI, S
中科院分区：
文献类型：
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作者：
GOTO, Y;NONAKA, I;HORAI, S
线粒体脑肌病通常分为三个不同的临床亚型：(1)线粒体肌病、脑病、乳酸酸中毒和卒中样发作(MELAS)；(2)肌阵挛癫痫伴不整红色纤维(MERRF)；(3)慢性进行性眼外肌麻痹(CPEO)，包括Kearns-Sayre综合征1-5。人类线粒体DNA的大量缺失和线粒体转移RNAlys基因的过渡性突变分别导致CPEO，包括Kearns-Sayre综合征6-8和MERRF9，10。在这里，我们报告了线粒体tRNALeu(UUR)二氢尿苷环上3,243核苷酸对A到G的转换突变，这是MELAS患者特有的。因为这种突变产生了Apal限制酶切位点，所以我们可以对这种疾病进行简单的分子诊断测试。在31名独立的MELAS患者中有26名患者和29名CPEO患者中有1名患者存在该突变，但在5名MERRF患者和50名对照组中未发现该突变。Southern杂交分析证实，突变体DNA始终与野生型DNA共存(异质性)。
MITOCHONDRIAL encephalomyopathies are usually divided into three distinct clinical subgroups: (1) mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS); (2) myoclonus epilepsy associated with ragged-red fibres (MERRF); and (3) chronic progressive external ophthalmoplegia (CPEO) including Kearns-Sayre syndrome1–5. Large deletions of human mitochondrial DNA and a transition mutation at the mitochondrial transfer RNAlysgene give rise to CPEO including Kearns–Sayre syndrome6–8and MERRF9,10, respectively. Here we report an A-to-G transition mutation at nucleotide pair 3,243 in the dihydrouridine loop of mitochondrial tRNALeu(UUR)that is specific to patients with MELAS. Because this mutation creates anApal restriction site, we could perform a simple molecular diagnostic test for the disease. The mutation was present in 26 out of 31 independent MELAS patients and 1 out of 29 CPEO patients, but absent in the 5 MERRF and 50 controls tested. Southern blot analysis confirmed that the mutant DNA always coexists with the wild-type DNA (heteroplasmy).