Related Experiment Videos
Mitochondrial DNA analysis in ocular myopathy. Observations in 29 Portuguese patients
L Vilarinho1, F M Santorelli, M L Cardoso
1Department of Clinical Biology, Instituto de Genética Médica, Porto, Portugal.
Abstract:
We analyzed 29 patients with progressive external ophthalmoparesis (PEO) either alone or as part of a multisystem disorder. Ragged-red fibers were very abundant (10-20%) in 15 patients, and many of them were also cytochrome c oxidase-negative. Biochemical analysis of the respiratory chain showed partial defects of single or multiple complexes in 18 patients (64%). Eleven PEO patients (38%) harbored single large-scale mtDNA deletions in muscle, which averaged 5.4 kb in size and 47% in relative abundance. One PEO patient harbored the A3243G mutation (MELAS mutation) in muscle (63%). Our findings, the first reported in Portuguese patients, confirm that single large-scale mtDNA deletions are a significant cause of PEO. Although ophthalmoparesis was the main clinical feature in the majority of patients, the clinical spectrum is broad, ranging from severe encephalopathy of childhood to a milder, though disabling, muscle weakness in adults.
Insights
Single large-scale mitochondrial DNA deletions are a key cause of progressive external ophthalmoparesis (PEO) in Portuguese patients. This study highlights the broad clinical spectrum of PEO, from childhood encephalopathy to adult muscle weakness.
Area of Science:
- Neurology
- Genetics
- Mitochondrial Diseases
Background:
- Progressive external ophthalmoparesis (PEO) can be a primary condition or part of a multisystem disorder.
- Mitochondrial dysfunction is implicated in various neuromuscular diseases.
Purpose of the Study:
- To investigate the genetic and biochemical causes of PEO in Portuguese patients.
- To determine the prevalence of mitochondrial DNA (mtDNA) abnormalities in PEO.
Main Methods:
- Analysis of 29 patients with PEO.
- Muscle biopsy examination for ragged-red fibers and cytochrome c oxidase activity.
- Biochemical analysis of respiratory chain complexes.
- Molecular genetic testing for mtDNA deletions and mutations.
Main Results:
- 18 patients (64%) showed partial defects in respiratory chain complexes.
- 11 patients (38%) had single large-scale mtDNA deletions (average size 5.4 kb).
- One patient had the A3243G (MELAS) mutation.
Conclusions:
- Single large-scale mtDNA deletions are a significant cause of PEO in the studied Portuguese cohort.
- PEO presents a broad clinical spectrum, affecting individuals from childhood to adulthood.
- Mitochondrial defects are common in PEO patients.