Abstract
A young, adult, African male patient presented with progressive proximal muscle weakness, external ophthalmoplegia and ptosis, as well as cardiac conduction abnormalities resembling Kearns-Sayre syndrome (KSS). Magnetic resonance imaging (MRI) of the brain revealed normal basal ganglia but bilateral well-circumscribed lesions in the cerebellar peduncles. Enzyme deficiencies in oxidative phosphorylation (OXPHOS) complexes I, IV and V was measured in muscle tissue. Blue native polyacrylamide gel electrophoresis (BN-PAGE) confirmed decreased protein content and activity of these complexes and revealed the presence of two catalytically active complex V sub-complexes. Upon investigation by molecular genetics, the mitochondrial DNA (mtDNA) copy number was found to be elevated and a novel deletion of 3431 bp was found in 80% of muscle mtDNA between positions 7115 and 10546, flanked by a 5 bp direct repeat sequence. In addition, it could also be concluded that the absence of mtDNA-encoded ATPase6 and ATPase8 genes in this patient clearly resulted in aberrant synthesis of ATP synthase.
Publication types
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Case Reports
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Research Support, Non-U.S. Gov't
MeSH terms
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Black or African American / genetics*
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DNA Mutational Analysis
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DNA, Mitochondrial / genetics*
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Electron Transport Chain Complex Proteins / genetics
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Electrophoresis, Polyacrylamide Gel
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Energy Metabolism / genetics
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Genetic Predisposition to Disease
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Genetic Testing / methods
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Humans
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Magnetic Resonance Imaging
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Male
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Mitochondrial Proton-Translocating ATPases / genetics*
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Ophthalmoplegia, Chronic Progressive External / diagnosis
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Ophthalmoplegia, Chronic Progressive External / enzymology
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Ophthalmoplegia, Chronic Progressive External / ethnology
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Ophthalmoplegia, Chronic Progressive External / genetics*
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Oxidative Phosphorylation
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Phenotype
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Sequence Deletion*
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Young Adult
Substances
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DNA, Mitochondrial
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Electron Transport Chain Complex Proteins
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MT-ATP6 protein, human
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MT-ATP8 protein, human
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Mitochondrial Proton-Translocating ATPases
Associated data
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OMIM/180104
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OMIM/258400
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OMIM/258450
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OMIM/268000
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OMIM/268025
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OMIM/300389
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OMIM/312600
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OMIM/312612
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OMIM/500004
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OMIM/608133
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OMIM/609283
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OMIM/609286
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OMIM/610131
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OMIM/612572
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OMIM/OMIM157640
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OMIM/OMIM530000
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OMIM/OMIM557000
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OMIM/OMIM600105