Multiple mitochondrial DNA deletions in monozygotic twins with OPMD

• Published in: Journal of neurology, neurosurgery and psychiatry Vol. 79; no. 1; pp. 68 - 71
• Main Authors: Muqit, M M K, Larner, A J, Sweeney, M G, Sewry, C, Stinton, V J, Davis, M B, Healy, D G, Payne, S J, Chotai, K, Wood, N W, Lane, R J M
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01.01.2008; BMJ; BMJ Publishing Group LTD
• Subjects: Aged; Aging; Biological and medical sciences; Biopsy; Blotting, Southern; Deafness; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Deoxyribonucleic acid; DNA; DNA Mutational Analysis; DNA, Mitochondrial - genetics; Dysphagia; Ear diseases; Gene Deletion; Gene expression; Humans; Kinases; Male; Medical sciences; Mitochondria; Mitochondrial DNA; monozygotic; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Muscle, Skeletal - pathology; Muscular Dystrophy, Oculopharyngeal - genetics; Muscular Dystrophy, Oculopharyngeal - pathology; Mutation; myopathy; Neurology; OPMD; Pathology; Phenotype; Point Mutation - genetics; Poly(A)-Binding Protein II - genetics; Polymerase Chain Reaction; Proteins; Studies; Twins; Twins, Monozygotic - genetics; Deletion; Nervous system diseases; Mitochondrial DNA; Monozygotic twin
• ISSN: 0022-3050; 1468-330X
• DOI: 10.1136/jnnp.2006.112250

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 muscles 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 with markedly different severities 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, which might 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.