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.