一名具有肌阵挛性癫痫伴破碎红纤维综合征（MERRF）和卡恩斯-塞尔综合征（Kearns-Sayre syndrome）特征的患者中发现一种新的线粒体tRNA（Leu（UUR））突变。

A novel mitochondrial tRNA(Leu(UUR)) mutation in a patient with features of MERRF and Kearns-Sayre syndrome.

作者信息

Nishigaki Yutaka, Tadesse Saba, Bonilla Eduardo, Shungu Dikoma, Hersh Stephen, Keats Bronya J B, Berlin Charles I, Goldberg Morton F, Vockley Jerry, DiMauro Salvatore, Hirano Michio

机构信息

Department of Neurology, Columbia University College of Physicians and Surgeon, 630 West 168th Street, P&S 4-443, New York, NY 10032, USA.

出版信息

Neuromuscul Disord. 2003 May;13(4):334-40. doi: 10.1016/s0960-8966(02)00283-3.

DOI:10.1016/s0960-8966(02)00283-3

PMID:12868503

Abstract

In a patient with clinical features of both myoclonus epilepsy ragged-red fibers (MERRF) and Kearns-Sayre syndrome (KSS), we identified a novel guanine-to-adenine mitochondrial DNA (mtDNA) mutation at nucleotide 3255 (G3255A) of the tRNA(Leu(UUR)) gene. Approximately 5% of the skeletal muscle fibers had excessive mitochondria by succinate dehydrogenase histochemistry while a smaller proportion showed cytochrome c oxidase (COX) deficiency. In skeletal muscle, activities of mitochondrial respiratory chain complexes I, I + III, II + III, and IV were reduced. The G3255A transition was heteroplasmic in all tissues tested: muscle (53%), urine sediment (67%), peripheral leukocytes (22%), and cultured skin fibroblasts (< 2%). The mutation was absent in 50 control DNA samples. Single-fiber analysis revealed a higher proportion of mutation in COX-deficient RRF (94% +/- 5, n = 25) compared to COX-positive non-RRF (18% +/- 9, n = 21). The identification of yet another tRNA(Leu(UUR)) mutation reinforces the concept that this gene is a hot-spot for pathogenic mtDNA mutations.

摘要

在一名具有肌阵挛性癫痫伴破碎红纤维（MERRF）和凯-塞尔综合征（KSS）临床特征的患者中，我们在tRNA(Leu(UUR))基因的第3255位核苷酸（G3255A）处鉴定出一种新的鸟嘌呤到腺嘌呤的线粒体DNA（mtDNA）突变。通过琥珀酸脱氢酶组织化学检测，约5%的骨骼肌纤维含有过多的线粒体，而较小比例的纤维显示细胞色素c氧化酶（COX）缺乏。在骨骼肌中，线粒体呼吸链复合物I、I + III、II + III和IV的活性降低。G3255A转换在所有检测组织中均为异质性：肌肉（53%）、尿沉渣（67%）、外周血白细胞（22%）和培养的皮肤成纤维细胞（<2%）。在50份对照DNA样本中未发现该突变。单纤维分析显示，与COX阳性的非破碎红纤维（RRF）（18%±9，n = 21）相比，COX缺乏的RRF中突变比例更高（94%±5，n = 25）。又一个tRNA(Leu(UUR))突变的鉴定强化了该基因是致病性mtDNA突变热点的概念。