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Previously Unclassified Mutation of mtDNA m.3472T>C: Evidence of Pathogenicity in Leber’s Hereditary Optic Neuropathy

N. L. Sheremet1*, T. A. Nevinitsyna1, N. V. Zhorzholadze1, I. A. Ronzina1, Y. S. Itkis2, T. D. Krylova2, P. G. Tsygankova2, V. A. Malakhova2, E. Y. Zakharova2, A. V. Tokarchuk3, A. A. Panteleeva3, E. M. Karger3, K. G. Lyamzaev3*, and S. E. Avetisov1

1Research Institute of Eye Diseases, 119021 Moscow, Russia; E-mail: sheremet_n@mail.ru

2Research Center for Medical Genetics, 115478 Moscow, Russia

3Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia; E-mail: lyamzaev@gmail.com

* To whom correspondence should be addressed.

Received March 21, 2016; Revision received April 8, 2016
Leber’s hereditary optic neuropathy (LHON) refers to a group of mitochondrial diseases and is characterized by defects of the mitochondrial electron transport chain and decreased level of oxidative phosphorylation. The list of LHON primary mtDNA mutations is regularly updated. In this study, we describe the homoplasmic nucleotide substitution m.3472T>C in the MT-ND1 (NADH-ubiquinone oxidoreductase chain 1) gene and specific changes in cell metabolism in a patient with LHON and his asymptomatic sister. To confirm the presence of mutation-related mitochondrial dysfunction, respiration of skin fibroblasts and platelets from the patient and his sister was studied, as well as the mitochondrial potential and production of reactive oxygen species in the skin fibroblasts. In addition, based on characteristics of the toxic effect of paraquat, a new approach was developed for detecting the functional activity of complex I of the mitochondrial respiratory chain.
KEY WORDS: Leber’s hereditary optic neuropathy, mtDNA mutations, respiratory chain complex I, fibroblasts

DOI: 10.1134/S0006297916070117