Amyotrophic lateral sclerosis linked to a novel SOD1 mutation with muscle mitochondrial dysfunction
Amyotrophic lateral sclerosis linked to a novel SOD1 mutation with muscle mitochondrial dysfunction
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DOI：
10.1016/j.jns.2008.09.030
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发表时间：
2009-01-15
影响因子：
4.4
通讯作者：
Comi, Giacomo P.
中科院分区：
文献类型：
--
作者：
Corti, Stefania;Donadoni, Chiara;Comi, Giacomo P.
肌萎缩侧索硬化症（ALS）是一种致命的神经退行性运动神经元疾病。Cu，Zn超氧化物歧化酶（SOD）的突变导致大约20%的家族性ALS。它们诱发疾病的可能机制之一是运动神经元中的线粒体功能障碍。在这里，我们描述了一个病人与肌萎缩侧索硬化症和肌肉线粒体氧化缺陷与一种新的超氧化物歧化酶1突变。SOD1基因的直接测序结果显示，在第22位密码子处发生了一个杂合突变，将一个高度保守的氨基酸从谷氨酰胺替换为精氨酸（Q22R）。肌肉活检显示与细胞色素c氧化酶（考克斯）缺乏相关的神经原性模式在几个肌纤维。Western印迹分析表明，细胞质和线粒体组分中的SOD 1含量减少。这些结果表明，微量的突变SOD 1蛋白也在肌肉组织中导致线粒体毒性。(C)2008 Elsevier B.V.保留所有权利。
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative motor neuron disorder. Mutations in Cu,Zn superoxide dismutase (SOD]) cause approximately 20% of familial ALS. One of the possible mechanisms whereby they induce disease is mitochondrial dysfunction in motor neurons. Here we describe a patient with ALS and muscle mitochondrial oxidative defect associated with a novel SOD1 Mutation. Direct sequencing of SOD1 gene revealed a heterozygous mutation in codon 22 substituting a highly conserved amino acid, from glutamine to arginine (Q22R). Muscle biopsy showed a neurogenic pattern associated with cytochrome c oxidase (COX) deficiency in several muscle fibers. Western blot analysis demonstrated a reduction in SOD1 content in the cytoplasmic and mitochondrial fractions. These results suggest that a minute quantity of mutant SOD1 protein contributes to a mitochondrial toxicity also in muscle tissue. (C) 2008 Elsevier B.V. All rights reserved.