Seibel P, Flierl A, Kottlors M, Reichmann H
Neurologische Klinik und Poliklinik, Julius-Maximilians-Universität, Würzburg, Germany.
Biochem Biophys Res Commun. 1994 Apr 29;200(2):938-42. doi: 10.1006/bbrc.1994.1540.
Alterations of the mitochondrial DNA, encoding important parts of the cellular energy-generating system (oxidative phosphorylation, OXPHOS), are often associated with the occurrence of degenerative neuromuscular diseases. Especially point mutations in the mitochondrial tRNA genes, which cannot be complemented by the nuclear encoded tRNAs, are candidates for severe defects of the OXPHOS system. An A to G transition at nt 8344 in the tRNA(Lys) gene has been associated with MERRF disease whereas an A to G substitution at nt 3243 in the tRNA(Leu) gene has been linked to the MELAS syndrome. These two mtDNA alterations as well as point mutations in protein-coding genes can be detected simultaneously by an allele-specific amplification of the altered mtDNA. This assay allows the reliable detection of heteroplasmic point-mutations, even if the mutated DNA appears to a small extent of less than 1%.
线粒体DNA的改变，编码细胞能量产生系统（氧化磷酸化，OXPHOS）的重要部分，通常与退行性神经肌肉疾病的发生有关。特别是线粒体tRNA基因中的点突变，不能由核编码的tRNA互补，是OXPHOS系统严重缺陷的候选因素。tRNA（Lys）基因第8344位核苷酸由A到G的转换与肌阵挛性癫痫伴破碎红纤维病（MERRF）相关，而tRNA（Leu）基因第3243位核苷酸由A到G的替换与线粒体脑肌病伴乳酸血症和卒中样发作综合征（MELAS）相关。通过改变的线粒体DNA的等位基因特异性扩增，可以同时检测这两种线粒体DNA改变以及蛋白质编码基因中的点突变。该检测方法能够可靠地检测异质性点突变，即使突变的DNA出现的比例小至不到1%。
