Respiratory chain complex V deficiency due to a mutation in the assembly gene ATP12
Respiratory chain complex V deficiency due to a mutation in the assembly gene ATP12
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DOI：
10.1136/jmg.2003.012047
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发表时间：
2004-02-01
影响因子：
4
通讯作者：
Van Coster, R
中科院分区：
文献类型：
--
作者：
De Meirleir, L;Seneca, S;Van Coster, R
在线粒体脑肌病患者中，已检测到越来越多的致病基因缺陷。在过去的15年中，已确定的致病性线粒体DNA突变的数量大大增加。核氧化磷酸化（OXPHOS）基因缺陷是近年来研究的热点。在OXPHOS缺陷中，复合物V缺陷很少被发现，并且到目前为止，这些缺陷仅归因于线粒体MTATP 6基因的突变。在两个无关患者中进行了核ATP 11、ATP 12、ATP α、ATP β和ATP γ基因以及线粒体MTATP 6和MTAT 8基因的cDNA水平的完整编码区的突变分析。蓝色聚丙烯酰胺凝胶电泳后，催化染色已经证明他们的复合物V活性降低。广泛的5个核基因和线粒体基因的分子分析显示，在一个病人的ATP 12组装基因的突变。这种突变被认为是复合物V活性受损的原因。据我们所知，这是首次报道人类核编码ATP酶组装基因发生致病突变。
In patients with mitochondrial encephalomyopathies an increasing number of causative gene defects have been detected. The number of identified pathogenic mitochondrial DNA mutations has largely increased over the past 15 years. Recently, much attention has turned to the investigation of nuclear oxidative phosphorylation (OXPHOS) gene defects. Within the OXPHOS defects, complex V deficiency is rarely found and, so far, these defects have only been attributed to mutations in the mitochondrial MTATP6 gene.Mutation analysis of the complete coding regions at the cDNA level of the nuclear ATP11, ATP12, ATPalpha, ATPbeta and ATPgamma genes and the mitochondrial MTATP6 and MTAT8 genes was undertaken in two unrelated patients. Blue Native polyacrylamide gel electrophoresis followed by catalytic staining had already documented their complex V decreased activity.Extensive molecular analysis of five nuclear and two mitochondrial genes revealed a mutation in the ATP12 assembly gene in one patient. This mutation is believed to be the cause of the impaired complex V activity. To our knowledge, this is the first report of a pathogenic mutation in a human nuclear encoded ATPase assembly gene.