MELAS-like encephalomyopathy caused by a new pathogenic mutation in the mitochondrial DNA encoded cytochrome c oxidase subunit I

Costanza Lamperti, Daria Diodato, Eleonora Lamantea, Franco Carrara, Daniele Ghezzi, Paolo Mereghetti, Romana Rizzi, Massimo Zeviani

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)990-994
Number of pages5
JournalNeuromuscular Disorders
Volume22
Issue number11
DOIs
Publication statusPublished - Nov 2012

Keywords

  • COX
  • Cytochrome c oxidase
  • MELAS
  • Mitochondrial disorder
  • MTCOI
  • MtDNA
  • Mutation
  • Ragged-red fibers
  • Respiratory chain
  • SDH
  • Stroke-like episode

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health
  • Genetics(clinical)
  • Neurology

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