Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Foundation Ospedale Maggiore Policlinico, Mangiagalli and Regina Elena, Milan, Italy.
J Neurol Sci. 2010 May 15;292(1-2):107-10. doi: 10.1016/j.jns.2010.01.026. Epub 2010 Feb 18.
Mitochondrial disorders are often associated with mutations in mitochondrial tRNA. Independent observation of the same molecular defect in unrelated subjects is a generally required proof of pathogenicity. A sporadic case of chronic external ophthalmoplegia (cPEO) with ragged red fibres (RRFs) has been previously related to an m.12316G>A substitution in tRNA(Leu(CUN)). Sequencing muscle-derived mtDNA, we found the m.12316G>A substitution in an adult woman with mitochondrial myopathy and respiratory impairment. Her muscle biopsy presented several cytochrome c oxidase-negative (COX-) fibres, and RRFs as signs of mitochondrial proliferation. Restriction-fragment length polymorphism (RFLP) analysis of the mutation in isolated muscle fibres showed a threshold of at least 60% of mutated mtDNA to determine a COX deficiency phenotype. This second report of the m.12316G>A mutation in a sporadic patient consolidates its pathogenic nature and provides further elements for genetic counselling.
线粒体疾病通常与线粒体 tRNA 的突变有关。在无关联的个体中独立观察到相同的分子缺陷是致病性的一般必需证据。先前已有一例散发性慢性外眼肌麻痹（cPEO）伴红纤维（RRF）与 tRNA(Leu(CUN))的 m.12316G>A 取代有关。我们对一位患有线粒体肌病和呼吸功能障碍的成年女性的肌肉源性 mtDNA 进行测序，发现了 m.12316G>A 取代。她的肌肉活检显示出一些细胞色素 c 氧化酶阴性（COX-）纤维和 RRF，这是线粒体增殖的标志。对分离的肌肉纤维中突变的限制性片段长度多态性（RFLP）分析表明，至少有 60%的突变 mtDNA 可确定 COX 缺乏表型。这例散发性患者中 m.12316G>A 突变的再次报道证实了其致病性，并为遗传咨询提供了更多依据。
