De novo mutations in the mitochondrial ND3 gene as a cause of infantile mitochondrial encephalopathy and complex I deficiency

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dc.contributor.authorMcFarland, R.
dc.contributor.authorKirby, D.
dc.contributor.authorFowler, K.
dc.contributor.authorOhtake, A.
dc.contributor.authorRyan, M.
dc.contributor.authorAmor, D.
dc.contributor.authorFletcher, J.
dc.contributor.authorDixon, J.
dc.contributor.authorCollins, F.
dc.contributor.authorTurnbull, D.
dc.contributor.authorTaylor, R.
dc.contributor.authorThorburn, A.
dc.date.issued2004
dc.description.abstractBoth nuclear and mitochondrial DNA mutations can cause energy generation disorders. Respiratory chain complex I deficiency is the most common energy generation disorder and a frequent cause of infantile mitochondrial encephalopathies such as Leigh's disease and lethal infantile mitochondrial disease. Most such cases have been assumed to be caused by nuclear gene defects, but recently an increasing number have been shown to be caused by mutations in the mitochondrially encoded complex I subunit genes ND4, ND5, and ND6. We report the first four cases of infantile mitochondrial encephalopathies caused by mutations in the ND3 subunit gene. Three unrelated children have the same novel heteroplasmic mutation (T10158C), only the second mutation reported in ND3, and one has the previously identified T10191C mutation. Both mutations cause disproportionately greater reductions in enzyme activity than in the amount of fully assembled complex I, suggesting the ND3 subunit plays an unknown but important role in electron transport, proton pumping, or ubiquinone binding. Three cases appear to have a de novo mutation, with no mutation detected in maternal relatives. Mitochondrial DNA disease may be considerably more prevalent in the pediatric population than currently predicted and should be considered in patients with infantile mitochondrial encephalopathies and complex I deficiency.
dc.identifier.citationAnnals of Neurology, 2004; 55(1):58-64
dc.identifier.doi10.1002/ana.10787
dc.identifier.issn0364-5134
dc.identifier.issn1531-8249
dc.identifier.urihttp://hdl.handle.net/2440/6953
dc.language.isoen
dc.publisherWiley-Liss
dc.source.urihttp://www3.interscience.wiley.com/journal/106568802/abstract
dc.subjectMuscle, Skeletal
dc.subjectHumans
dc.subjectMitochondrial Encephalomyopathies
dc.subjectLeigh Disease
dc.subjectElectron Transport Complex I
dc.subjectProteins
dc.subjectDNA, Mitochondrial
dc.subjectBlotting, Western
dc.subjectPolymerase Chain Reaction
dc.subjectDNA Mutational Analysis
dc.subjectMutation
dc.subjectPolymorphism, Restriction Fragment Length
dc.subjectInfant, Newborn
dc.subjectFemale
dc.subjectMale
dc.titleDe novo mutations in the mitochondrial ND3 gene as a cause of infantile mitochondrial encephalopathy and complex I deficiency
dc.typeJournal article
pubs.publication-statusPublished

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