Ozawa M, Nishino I, Horai S, Nonaka I, Goto Y I
Department of Laboratory Medicine, National Center Hospital for Mental, Nervous and Muscular Disorders, Tokyo, Japan.
Muscle Nerve. 1997 Mar;20(3):271-8. doi: 10.1002/(SICI)1097-4598(199703)20:3<271::AID-MUS2>3.0.CO;2-8.
In addition to well-known mutations at nucleotide pair 8344 and 8356 in mitochondrial DNA in patients with myoclonus epilepsy associated with ragged-red fibers (MERRF), we found a new G-to-A point mutation at nucleotide 8363 in two Japanese families. The probands had the typical clinical characteristics of MERRF. Since the 8363 mutation was present in a heteroplasmic state, and seen in none of 92 patients with other mitochondrial diseases or 50 normal individuals, this mutation is thought to be disease-related and probably specific to MERRF. As seen in muscle biopsies with the previous two mutations, focal cytochrome c oxidase (CCO) deficiency was the most characteristic finding. With single fiber analysis, the CCO-negative fibers contained a higher percentage of mutant DNA (88.4 +/- 6.6%) than CCO-positive fibers (65.1 +/- 8.0%). These findings suggest that mutations in tRNA(Lys) coding region are related to the MERRF phenotype and are responsible for the reduced CCO activity.
除了肌阵挛性癫痫伴破碎红纤维（MERRF）患者线粒体DNA中核苷酸对8344和8356处的已知突变外，我们在两个日本家族中发现了核苷酸8363处一个新的G到A点突变。先证者具有MERRF的典型临床特征。由于8363突变以异质性状态存在，且在92例其他线粒体疾病患者或50名正常个体中均未发现，因此该突变被认为与疾病相关，可能是MERRF特有的。正如在前两个突变的肌肉活检中所见，局灶性细胞色素c氧化酶（CCO）缺乏是最典型的发现。通过单纤维分析，CCO阴性纤维中突变DNA的百分比（88.4±6.6%）高于CCO阳性纤维（65.1±8.0%）。这些发现表明，tRNA（Lys）编码区的突变与MERRF表型相关，并导致CCO活性降低。
