Jonckheere An I, Hogeveen Marije, Nijtmans Leo, van den Brand Mariel, Janssen Antoon, Diepstra Heleen, van den Brandt Frans, van den Heuvel Bert, Hol Frans, Hofste Tom, Kapusta Livia, Dillmann U, Shamdeen M, Smeitink J, Smeitink J, Rodenburg Richard
Geert Grooteplein 10 PO Box 9101, 6500 HB Nijmegen, Netherlands.
BMJ Case Rep. 2009;2009. doi: 10.1136/bcr.07.2008.0504. Epub 2009 Jan 23.
To identify the biochemical and molecular genetic defect in a 16-year-old patient presenting with apical hypertrophic cardiomyopathy and neuropathy suspected for a mitochondrial disorder.Measurement of the mitochondrial energy-generating system (MEGS) capacity in muscle and enzyme analysis in muscle and fibroblasts were performed. Relevant parts of the mitochondrial DNA were analysed by sequencing.A homoplasmic nonsense mutation m.8529G→A (p.Trp55X) was found in the mitochondrial ATP8 gene in the patient's fibroblasts and muscle tissue. Reduced complex V activity was measured in the patient's fibroblasts and muscle tissue, and was confirmed in cybrid clones containing patient-derived mitochondrial DNAWe describe the first pathogenic mutation in the mitochondrial ATP8 gene, resulting in an improper assembly and reduced activity of the complex V holoenzyme.
为确定一名16岁表现为心尖肥厚型心肌病和疑似线粒体疾病所致神经病变患者的生化及分子遗传学缺陷。进行了肌肉中线粒体能量生成系统（MEGS）能力的测定以及肌肉和成纤维细胞中的酶分析。通过测序分析了线粒体DNA的相关部分。在患者的成纤维细胞和肌肉组织中发现线粒体ATP8基因存在纯合无义突变m.8529G→A（p.Trp55X）。在患者的成纤维细胞和肌肉组织中检测到复合物V活性降低，并在含有患者来源线粒体DNA的细胞杂交克隆中得到证实。我们描述了线粒体ATP8基因中的首个致病突变，该突变导致复合物V全酶组装不当且活性降低。
