A novel mitochondrial MTND5 frameshift mutation causing isolated complex I deficiency, renal failure and myopathy
A novel mitochondrial MTND5 frameshift mutation causing isolated complex I deficiency, renal failure and myopathy
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DOI：
10.1016/j.nmd.2009.10.010
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发表时间：
2010-02-01
影响因子：
2.8
通讯作者：
Taylor, Robert W.
中科院分区：
文献类型：
--
作者：
Alston, Charlotte L.;Morak, Monika;Taylor, Robert W.
孤立性复合体I缺乏症是儿科线粒体疾病中最常见的酶缺陷，可能是由于核编码的结构或组装基因或线粒体基因组的突变引起的。我们报告了一位以慢性肾功能衰竭、肌病和持续性乳酸酸中毒为主要临床表现的年轻女孩的临床、生化和分子遗传学资料。由于MTND5基因的一个新突变(m.12425delA)，在肌肉中发现了一个孤立的复合体I缺乏症。这种单核苷酸缺失是异质性的，在先证者的几个组织中可以检测到，但她的母亲没有，这表明发生了从头开始的突变事件。线粒体复合体I基因第一个移码突变的描述肯定了线粒体DNA突变是儿童孤立复合体I缺乏症的重要原因，以及线粒体全基因组测序在诊断工作中的重要性，以阐明潜在的分子遗传异常并提供重要的遗传学建议。(C)2009爱思唯尔B.V.保留所有权利。
Isolated complex I deficiency is the most commonly reported enzyme defect in paediatric mitochondrial disorders, and may arise due to mutations in nuclear-encoded structural or assembly genes, or the mitochondrial genome. We present the clinical, biochemical and molecular genetic data in a young girl whose clinical picture is dominated by chronic renal failure, myopathy and persistent lactic acidosis. An isolated complex I deficiency in muscle was identified due to a novel mutation (m.12425delA) in the MTND5 gene. This single nucleotide deletion is heteroplasmic and detectable in several tissues from the proband but not her mother, suggesting a de novo Mutation event. The description of the first frameshift mutation in a mitochondrial complex I gene affirms mitochondrial DNA mutations as an important cause of isolated complex I deficiency in children and the importance of whole mitochondrial genome sequencing in the diagnostic work-up to elucidate the underlying molecular genetic abnormality and provide important genetic advice. (C) 2009 Elsevier B.V. All rights reserved.