Laforêt P, Eymard B, Danan C, Chevallay M, Rouche A, Frachon P, Fardeau M, Lombès A
INSERM U 153, Institut de Myologie.
Rev Neurol (Paris). 1997 Feb;153(1):51-8.
We performed a comparative analysis of the clinical, morphological and molecular characteristics of 62 patients affected with progressive external ophthalmoplegia with ragged-red fibres in muscle. Twenty-seven patients had only muscular disease, and 35 had a multisystemic disease with neurological, cardiac, sensory, or endocrine symptoms. Quantitation of mitochondrial accumulation and numbering of cytochrome c oxidase deficient muscle fibres were done in 43 patients. Muscle mitochondrial DNA deletions were detected, quantitated and localised by Southern Blot analysis. Point mutations were screened in five mitochondrial DNA transfer RNA genes by denaturing gradient gel electrophoresis technique. This study further emphasized the relationships between progressive external ophthalmoplegia and mitochondrial DNA mutations that were present in 46/62 patients (40 deletions, 4 h point mutations in the tRNA leucine gene and 2 further families with maternal inheritance but no mutation identified to-date). Family history was positive in 12 patients: 4 with a maternally inherited disease (2 of whom had an identified mitochondrial DNA mutation), and 4 with an autosomal dominant inherited disease, none of which was associated with multiple mitochondrial DNA deletions. Interestingly, 2 of our patients with an identified mitochondrial DNA mutation appeared as sporadic cases. No morphological or molecular parameters was correlated with the tissular extension of the disease. However, mitochondrial DNA deletions were significantly associated with ocular symptoms which had an earlier onset and were more severe. Clinical features of the patients with a multisystemic disease and a mitochondrial DNA deletion were essentially related to Kearns-Sayre syndrome. In particular, a cardiac conduction defect was present in 12 patients out of 18 with a multisystemic disease associated with a mitochondrial DNA deletion; it was never encountered in 17 patients with a multisystemic disease but no mitochondrial DNA deletion.
我们对62例患有进行性眼外肌麻痹且肌肉中有破碎红纤维的患者的临床、形态学和分子特征进行了比较分析。27例患者仅有肌肉疾病，35例有多系统疾病，伴有神经、心脏、感觉或内分泌症状。对43例患者进行了线粒体积累定量和细胞色素c氧化酶缺陷肌纤维计数。通过Southern印迹分析检测、定量和定位肌肉线粒体DNA缺失。通过变性梯度凝胶电泳技术在五个线粒体DNA转移RNA基因中筛选点突变。本研究进一步强调了进行性眼外肌麻痹与线粒体DNA突变之间的关系，46/62例患者（40例缺失、4例tRNA亮氨酸基因中的点突变以及另外2个有母系遗传但迄今未发现突变的家系）存在这种关系。12例患者家族史呈阳性：4例患有母系遗传疾病（其中2例已鉴定出线粒体DNA突变），4例患有常染色体显性遗传疾病，均与多个线粒体DNA缺失无关。有趣的是，我们2例已鉴定出线粒体DNA突变的患者表现为散发病例。没有形态学或分子参数与疾病的组织扩展相关。然而，线粒体DNA缺失与眼部症状显著相关，眼部症状发病更早且更严重。患有多系统疾病和线粒体DNA缺失的患者的临床特征主要与Kearns-Sayre综合征相关。特别是，18例患有与线粒体DNA缺失相关的多系统疾病的患者中有12例存在心脏传导缺陷；17例患有多系统疾病但没有线粒体DNA缺失的患者从未出现过这种情况。
