Goto Y, Nonaka I, Horai S
Division of Ultrastructural Research, National Center of Neurology and Psychiatry, Tokyo, Japan.
Nature. 1990 Dec 13;348(6302):651-3. doi: 10.1038/348651a0.
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 syndrome. Large deletions of human mitochondrial DNA and a transition mutation at the mitochondrial transfer RNALys gene give rise to CPEO including Kearns-Sayre syndrome and MERRF, respectively. Here we report an A-to-G transition mutation at nucleotide pair 3,243 in the dihydrouridine loop of mitochondrial tRNA(Leu)(UUR) that is specific to patients with MELAS. Because this mutation creates an ApaI 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).
（1）线粒体肌病、脑病、乳酸酸中毒和卒中样发作（MELAS）；（2）伴有破碎红纤维的肌阵挛癫痫（MERRF）；（3）慢性进行性眼外肌麻痹（CPEO），包括卡恩斯-塞尔综合征。人类线粒体DNA的大片段缺失和线粒体赖氨酸转运RNA基因的一个转换突变分别导致了包括卡恩斯-塞尔综合征的CPEO和MERRF。在此，我们报告了线粒体tRNA（Leu）（UUR）二氢尿嘧啶环中第3243位核苷酸对由A到G的转换突变，该突变是MELAS患者所特有的。由于此突变产生了一个ApaI限制性酶切位点，我们能够对该疾病进行简单的分子诊断检测。该突变存在于31例独立的MELAS患者中的26例以及29例CPEO患者中的1例，但在检测的5例MERRF患者和50例对照中未出现。Southern印迹分析证实突变DNA总是与野生型DNA共存（异质性）。
