Molecular Genetics and Metabolism Reports (Mar 2017)

Pure myopathy with enlarged mitochondria associated to a new mutation in MTND2 gene

  • Alice Zanolini,
  • Ana Potic,
  • Franco Carrara,
  • Eleonora Lamantea,
  • Daria Diodato,
  • Flavia Blasevich,
  • Silvia Marchet,
  • Marina Mora,
  • Francesco Pallotti,
  • Lucia Morandi,
  • Massimo Zeviani,
  • Costanza Lamperti

DOI
https://doi.org/10.1016/j.ymgmr.2016.11.009
Journal volume & issue
Vol. 10, no. C
pp. 24 – 27

Abstract

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To date, only few mutations in the mitochondrial DNA (mtDNA)-encoded ND2 subunit of Complex I have been reported, usually presenting a severe phenotype characterized by early onset encephalomyopathy and early death. In this report, we describe a new mutation in the MTND2 gene in a 21-year-old man with a mild myopathic phenotype characterized by exercise intolerance and increased plasma lactate at rest. Electromyography and brain NMR were normal, and no cardiac involvement was present. Muscle biopsy showed a massive presence of ragged red – COX-positive fibres, with enlarged mitochondria containing osmiophilic inclusions. Biochemical assays revealed a severe isolated complex I deficiency. We identified a novel, heteroplasmic mutation m.4831G>A in the MTND2 gene, causing the p.Gly121Asp substitution in the ND2 protein. The mutation was present in the 95% of mitochondrial genomes from patient's muscle tissue, at a lower level in cells from the urinary tract and at a lowest level in lymphocytes from patient's blood; the base substitution was absent in fibroblasts and in the tissues from proband's healthy mother and brother. The specific skeletal muscle tissue involvement can explain the childhood-onset and the relatively benign, exclusively myopathic course of the disease.

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