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Elsevier, BBA - Molecular Basis of Disease, 3(1832), p. 445-452, 2013

DOI: 10.1016/j.bbadis.2012.12.002

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Cybrid studies establish the causal link between the mtDNA m.3890G>A/MT-ND1 mutation and optic atrophy with bilateral brainstem lesions

Journal article published in 2013 by Leonardo Caporali, Anna Maria Ghelli, Luisa Iommarini, Alessandra Maresca ORCID, Maria Lucia Valentino, Chiara La Morgia ORCID, Rocco Liguori, Claudia Zanna, Piero Barboni, Vera De Nardo, Andrea Martinuzzi ORCID, Giovanni Rizzo, Caterina Tonon, Raffaele Lodi, Maria Antonietta Calvaruso and other authors.
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Abstract

Complex I (CI) deficiency is a frequent cause of mitochondrial disorders and, in most cases, is due to mutations in CI subunit genes encoded by mitochondrial DNA (mtDNA). In this study, we establish the pathogenic role of the heteroplasmic mtDNA m.3890G>A/MT-ND1 (p.R195Q) mutation, which affects an extremely conserved amino acid position in ND1 subunit of CI. This mutation was found in a young-adult male with optic atrophy resembling Leber's hereditary optic neuropathy (LHON) and bilateral brainstem lesions. The only previously reported case with this mutation was a girl with fatal infantile Leigh syndrome with bilateral brainstem lesions. Transfer of the mutant mtDNA in the cybrid cell system resulted in a marked reduction of CI activity and CI-dependent ATP synthesis in the presence of a normally assembled enzyme.