The G13513A mutation in the ND5 gene of mitochondrial DNA as a common cause of MELAS or Leigh syndrome -: Evidence from 12 cases
The G13513A mutation in the ND5 gene of mitochondrial DNA as a common cause of MELAS or Leigh syndrome -: Evidence from 12 cases
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DOI：
10.1001/archneurol.2007.67
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发表时间：
2008-03-01
影响因子：
--
通讯作者：
DiMauro, Salvatore
中科院分区：
文献类型：
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作者：
Shanske, Sara;Coku, Jorida;DiMauro, Salvatore
背景：MELAS（一种由线粒体脑肌病、乳酸性酸中毒和中风样发作组成的综合征）和 Leigh 综合征 (LS) 的分子原因数量稳步增加。其中，线粒体DNA ND5基因（OMIM 516005）突变很重要，A13513A变化已成为热点。 目的：描述12例线粒体DNA ND5基因G13513A突变患者与14例先前描述的相同突变患者的临床特征、肌肉病理和生化特征以及分子研究结果。设计：临床检查和形态学、生化和分子分析。地点：三级甲等大学医院和分子诊断实验室。患者：三名患者具有典型的 MELAS 综合征特征；结果：家族史提示少数病例有母系遗传；其余9例具有典型的LS临床和影像学特征。肌肉样本的形态学研究很少显示出典型的参差不齐的红色纤维，而更常见的是显示出强烈的琥珀酸脱氢酶反应性血管。从生化角度来看，复合物 I 缺乏是不一致的，而且通常是轻微的。肌肉和血液标本中的突变负荷相对较高。结论：G13513A突变是MELAS和LS的常见原因，即使在没有明显母系遗传、肌肉病理发现或严重复合物I缺乏的情况下也是如此。
Background: The number of molecular causes of MELAS (a syndrome consisting of mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes) and Leigh syndrome (LS) has steadily increased. Among these, mutations in the ND5 gene (OMIM 516005) of mitochondrial DNA are important, and the A13513A change has emerged as a hotspot.Objective: To describe the clinical features, muscle pathological and biochemical characteristics, and molecular study findings of 12 patients harboring the G13513A mutation in the ND5 gene of mitochondrial DNA compared with 14 previously described patients with the same mutation.Design: Clinical examinations and morphological, biochemical, and molecular analyses.Setting: Tertiary care university hospital and molecular diagnostic laboratory.Patients: Three patients had the typical syndrome features of MELAS; the other 9 had typical clinical and radiological features of LS.Results: Family history suggested maternal inheritance in a few cases; morphological studies of muscle samples rarely showed typical ragged-red fibers and more often exhibited strongly succinate dehydrogenase reactive blood vessels. Biochemically, complex I deficiency was inconsistent and generally mild. The mutation load was relatively high in the muscle and blood specimens.Conclusion: The G13513A mutation is a common cause of MELAS and LS, even in the absence of obvious maternal inheritance, pathological findings in muscle, or severe complex I deficiency.