title: MELAS-like encephalomyopathy caused by a new pathogenic mutation in the mitochondrial DNA encoded cytochrome c oxidase subunit I.
abstract: We report a 35-year-old woman presenting a stroke-like episode with transitory aphasia followed by generalized tonic-clonic seizures. She had severe hearing loss and suffered from frequent episodes of migraine. Although a brain MRI disclosed a T2-hyperintense lesion in the left parietal lobe, she had hardly any long-term sequela. Exercise intolerance, myalgias and limb-girdle muscle weakness indicated a slowly progressive myopathy. Extra-neurological features included short stature, and secondary amenorrhea with low gonadotropin levels, indicating secondary hypogonadism. However, she had three mutation-free, healthy children by ovarian stimulation. A muscle biopsy showed ragged-red, cytochrome c oxidase-negative fibers, and an isolated defect of cytochrome c oxidase activity in muscle mitochondria. Sequence analysis of muscle mtDNA revealed a previously unreported heteroplasmic m.6597C>A transversion in the MTCOI gene, encoding subunit I of cytochrome c oxidase, corresponding to p.Q232K aminoacid change. Analysis on transmitochondrial cybrids demonstrated that the mutation is indeed associated with COX deficiency, i.e. pathogenic.
authors: Unit of Molecular Neurogenetics, Fondazione Istituto Neurologico Carlo Besta - IRCCS, via Temolo 4, 20126 Milano, Italy.
authors: Costanza
authors: C
authors: Lamperti
authors: Daria
authors: D
authors: Diodato
authors: Eleonora
authors: E
authors: Lamantea
authors: Franco
authors: F
authors: Carrara
authors: Daniele
authors: D
authors: Ghezzi
authors: Paolo
authors: P
authors: Mereghetti
authors: Romana
authors: R
authors: Rizzi
authors: Massimo
authors: M
authors: Zeviani
mesh_terms: D030401:Cytochrome-c Oxidase Deficiency / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D018450:Disease Progression; D003576:Electron Transport Complex IV / Q000235:genetics*; D005260:Female; D006801:Humans; D017241:MELAS Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D009135:Muscular Diseases / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D021122:Protein Subunits / Q000235:genetics; D012640:Seizures / Q000235:genetics / Q000473:pathology
chemical_list: D004272:DNA, Mitochondrial; D021122:Protein Subunits; D003576:Electron Transport Complex IV