Multiple mitochondrial DNA deletions in monozygotic twins with OPMD.
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.


CONCLUSIONS
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.
Muqit
M M K
MM
Division of Clinical Neurosciences and Psychological Medicine, Imperial College London, UK.
Larner
A J
AJ
Sweeney
M G
MG
Sewry
C
C
Stinton
V J
VJ
Davis
M B
MB
Healy
D G
DG
Payne
S J
SJ
Chotai
K
K
Wood
N W
NW
Lane
R J M
RJ
D000368:Aged; D001706:Biopsy; D015139:Blotting, Southern; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology; D039141:Muscular Dystrophy, Oculopharyngeal / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*; D039103:Poly(A)-Binding Protein II / Q000235:genetics*; D016133:Polymerase Chain Reaction; D014430:Twins, Monozygotic / Q000235:genetics*
D004272:DNA, Mitochondrial; D039103:Poly(A)-Binding Protein II