Is the mitochondrial complex I ND5 gene a hot-spot for MELAS causing mutations?

Authors

  • Danae Liolitsa PhD,

    1. Neuromuscular Unit, Institute of Neurology, University College London, United Kingdom
    2. Department of Molecular Pathogenesis, Institute of Neurology, University College London, United Kingdom
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  • Shamina Rahman PhD,

    1. Metabolic Unit, Institute of Child Health, Great Ormond Street Hospital, London, United Kingdom
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  • Sarah Benton FRCP,

    1. Department of Neurology, Great Ormond Street Hospital, London, United Kingdom
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  • Lucinda J. Carr MD,

    1. Department of Neurology, Great Ormond Street Hospital, London, United Kingdom
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  • Michael G. Hanna MD

    Corresponding author
    1. Neuromuscular Unit, Institute of Neurology, University College London, United Kingdom
    2. Department of Molecular Pathogenesis, Institute of Neurology, University College London, United Kingdom
    • Neuromuscular Unit and University Department of Molecular Pathogenesis, Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom
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Abstract

We identified two novel heteroplasmic mitochondrial DNA point mutations in the gene encoding the ND5 subunit of complex I: a 12770A→G transition identified in a patient with MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) and a 13045A→C transversion in a patient with a MELAS/Leber's hereditary optic neuropathy/Leigh's overlap syndrome. Biochemical analysis of muscle homogenates showed normal or very mildly reduced complex I activity. Histochemistry was normal. Our observations add to the evidence that mitochondrial ND5 protein coding gene mutations frequently associate with the MELAS phenotype, and it highlights the role of complex I dysfunction in MELAS. Ann Neurol 2003

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