Background: Oculopharyngeal muscular dystrophy (OPMD) is caused by expansions of the poly (A) binding protein 2 (PABP2) gene. Previous histological analyses have revealed mitochondrial abnormalities in the muscle of OPMD patients but their significance remains uncertain.
Objective: We had the rare opportunity to study monozygotic twins with identical expansions of the PABP2 gene but markedly different severity of OPMD. Both had histological features of mitochondrial myopathy. We determined whether mitochondrial DNA abnormalities underlay these changes.
Methods: Clinical information was obtained by history and examination. Muscle biopsies were obtained from each subject and genetic analysis was performed using long range PCR and Southern blotting.
Results: We demonstrate for the first time the presence of mitochondrial DNA (mtDNA) deletions by Southern blotting in individuals with OPMD. This correlates with the presence of mitochondrial myopathy in both twins. Moreover, both twins had different mtDNA deletions that may explain their phenotypic differences.
Conclusion: We hypothesise that mitochondrial dysfunction may occur as a consequence of PABP2 gene mutations, and that this dysfunction may affect the phenotypic manifestations of OPMD.
- PABP2 gene
- mitochondrial deletions
- monozygotic twins