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

TitlePure myopathy with enlarged mitochondria associated to a new mutation in MTND2 gene.
Publication TypeJournal Article
Year of Publication2017
AuthorsZanolini, A, Potic, A, Carrara, F, Lamantea, E, Diodato, D, Blasevich, F, Marchet, S, Mora, M, Pallotti, F, Morandi, L, Zeviani, M, Lamperti, C
JournalMol Genet Metab Rep
Date Published2017 Mar

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.

Alternate JournalMol Genet Metab Rep
Citation Key10.1016/j.ymgmr.2016.11.009
PubMed ID28070494
PubMed Central IDPMC5217772
Grant ListMC_UP_1002/1 / / Medical Research Council / United Kingdom