title: Mitochondrial encephalomyopathy with cytochrome c oxidase deficiency caused by a novel mutation in the MTCO1 gene.
abstract: Cytochrome c oxidase (COX) deficiency is one of the most common respiratory chain deficiencies. A woman was presented at the age of 18y with acute loss of consciousness, non-convulsive status epilepticus, slow neurological deterioration, transient cortical blindness, exercise intolerance, muscle weakness, hearing loss, cataract and cognitive decline. Muscle biopsy revealed ragged-red fibers, COX negative fibers and a significant decreased activity of complex IV in a homogenate. Using next generation massive parallel sequencing of the mtDNA, a novel heteroplasmic mutation was identified in MTCO1, m.7402delC, causing frameshift and a premature termination codon. Single fiber PCR showed co-segregation of high mutant load in COX negative fibers. Mutation in mitochondrially encoded complex IV subunits should be considered in mitochondrial encephalomyopathies and COX negative fibers after the common mtDNA mutations have been excluded.
authors: Metabolic Unit, Department of Medical Genetics, Sart-Tilman University Hospital, Domaine Sart-Tilman Bât B35, 4000 Liège, Belgium. Electronic address: fg.debray@chu.ulg.ac.be.
authors: François-Guillaume
authors: FG
authors: Debray
authors: Center of Medical Genetics, UZ Brussel and Reproduction and Genetics (REGE), Vrije Universiteit Brussel (VUB), 101 Laarbeeklaan, 1090 Brussels, Belgium.
authors: Sara
authors: S
authors: Seneca
authors: Department of Neurology, CHR Citadelle, 1 Boulevard XIIème de Ligne, 4000 Liège, Belgium.
authors: Michel
authors: M
authors: Gonce
authors: Center of Medical Genetics, UZ Brussel and Reproduction and Genetics (REGE), Vrije Universiteit Brussel (VUB), 101 Laarbeeklaan, 1090 Brussels, Belgium.
authors: Kim
authors: K
authors: Vancampenhaut
authors: Department of Neuropathology, Sart-Tilman University Hospital, Domaine Sart-Tilman Bât B35, 4000 Liège, Belgium.
authors: Elettra
authors: E
authors: Bianchi
authors: Metabolic Unit, Department of Medical Genetics, Sart-Tilman University Hospital, Domaine Sart-Tilman Bât B35, 4000 Liège, Belgium.
authors: François
authors: F
authors: Boemer
authors: Metabolic Unit, Department of Medical Genetics, Sart-Tilman University Hospital, Domaine Sart-Tilman Bât B35, 4000 Liège, Belgium.
authors: Laurent
authors: L
authors: Weekers
authors: Division of Pediatric Neurology and Metabolism, Department of Pediatrics, Ghent University Hospital, 185 De Pintelaan, 9000 Ghent, Belgium.
authors: Joél
authors: J
authors: Smet
authors: Division of Pediatric Neurology and Metabolism, Department of Pediatrics, Ghent University Hospital, 185 De Pintelaan, 9000 Ghent, Belgium.
authors: Rudy
authors: R
authors: Van Coster
mesh_terms: D000293:Adolescent; D001706:Biopsy; D018389:Codon, Nonsense; D030401:Cytochrome-c Oxidase Deficiency; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics; D003576:Electron Transport Complex IV / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D017237:Mitochondrial Encephalomyopathies / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D009132:Muscles / Q000473:pathology; D009154:Mutation
chemical_list: D018389:Codon, Nonsense; D004272:DNA, Mitochondrial; D003576:Electron Transport Complex IV; C581860:cytochrome c oxidase subunit I, human
keywords: Cytochrome c oxidase; Encephalomyopathy; MTCO1; Mitochondrial DNA