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Whereas the majority of disease-related mitochondrial DNA mutations exhibit significant biochemical and clinical heterogeneity, mutations within the mitochondrially encoded human cytochrome b gene (MTCYB) are almost exclusively associated with isolated complex III deficiency in muscle and a clinical presentation involving exercise intolerance. | ềFEBS Journal A mitochondrial cytochrome b mutation causing severe respiratory chain enzyme deficiency in humans and yeast Emma L. Blakely1 Anna L. Mitchell1 Nicholas Fisher2 Brigitte Meunier2 Leo G. Nijtmans3 Andrew M. Schaefer1 Margaret J. Jackson4 Douglass M. Turnbull1 and Robert W. Taylor1 1 MitochondrialResearch Group Schoolof Neurology Neurobiology and Psychiatry The MedicalSchool University of Newcastle upon Tyne UK 2 Wolfson Institute for BiomedicalResearch University College London UK 3 Nijmegen Center for MitochondrialDisorders Department of Pediatrics Radboud University Nijmegen MedicalCenter the Netherlands 4 Department of Neurology RoyalVictoria Infirmary Newcastle upon Tyne UK Keywords MitochondrialDNA mtDNA complex III complex I cytochrome b yeast mutants Correspondence R.W. Taylor MitochondrialResearch Group Schoolof Neurology Neurobiology and Psychiatry The Medical School Framlington Place University of Newcastle upon Tyne NE2 4HH UK Fax 44 191 2228553 Tel 44 191 2223685 E-mail r.w.taylor@ncl.ac.uk Received 15 April 2005 accepted 19 May 2005 doi 10.1111 j.1742-4658.2005.04779.x Whereas the majority of disease-related mitochondrial DNA mutations exhibit significant biochemical and clinical heterogeneity mutations within the mitochondrially encoded human cytochrome b gene MTCYB are almost exclusively associated with isolated complex III deficiency in muscle and a clinical presentation involving exercise intolerance. Recent studies have shown that a small number of MTCYB mutations are associated with a combined enzyme complex defect involving both complexes I and III on account of the fact that an absence of assembled complex III results in a dramatic loss of complex I confirming a structural dependence between these two complexes. We present the biochemical and molecular genetic studies of a patient with both muscle and brain involvement and a severe reduction in the activities of both complexes I and III in skeletal muscle due to a novel mutation in
