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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)24-27
Number of pages4
JournalMolecular Genetics and Metabolism Reports
Volume10
DOIs
Publication statusPublished - Dec 15 2016

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Muscular Diseases
Mitochondria
Mutation
Muscles
Genes
Phenotype
Mitochondrial Genome
Electromyography
Urinary Tract
Mitochondrial DNA
Siblings
Lactic Acid
Skeletal Muscle
Fibroblasts
Mothers
Lymphocytes
Exercise
Biopsy
Brain
Proteins

Keywords

  • Journal Article

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Pure myopathy with enlarged mitochondria associated to a new mutation in MTND2 gene. / Zanolini, Alice; Potic, Ana; Carrara, Franco; Lamantea, Eleonora; Diodato, Daria; Blasevich, Flavia; Marchet, Silvia; Mora, Marina; Pallotti, Francesco; Morandi, Lucia; Zeviani, Massimo; Lamperti, Costanza.

In: Molecular Genetics and Metabolism Reports, Vol. 10, 15.12.2016, p. 24-27.

Research output: Contribution to journalArticle

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AU - Zanolini, Alice

AU - Potic, Ana

AU - Carrara, Franco

AU - Lamantea, Eleonora

AU - Diodato, Daria

AU - Blasevich, Flavia

AU - Marchet, Silvia

AU - Mora, Marina

AU - Pallotti, Francesco

AU - Morandi, Lucia

AU - Zeviani, Massimo

AU - Lamperti, Costanza

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N2 - 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.

AB - 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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