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

Molecular Genetics and Metabolism Reports

Ana Potic¹  Francesco Pallotti²  Flavia Blasevich³  Lucia Morandi³  Marina Mora³  Eleonora Lamantea⁴  Massimo Zeviani⁴  Costanza Lamperti⁴  Franco Carrara⁴  Alice Zanolini⁴  Daria Diodato⁴  Silvia Marchet⁴ 

[1]Clinic for Child Neurology and Psychiatry, Department of Neurology, Medical Faculty University of Belgrade, Belgrade 11000, Serbia

[2]Dept of Surgical and Morphological Sciences, University of Insubria, Varese, Italy

[3]IV Division of Neurology, Fondazione IRCCS Istituto Neurologico ‘Carlo Besta’, 20126 Milan, Italy

[4]Unit of Molecular Neurogenetics, Fondazione IRCCS Istituto Neurologico ‘Carlo Besta’, 20126 Milan, Italy

关键词: ND2;    Exercise intolerance;    Complex I deficiency;   

DOI  :  10.1016/j.ymgmr.2016.11.009

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown