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Fifteen novel mutations in the mitochondrial NADH dehydrogenase subunit 1, 2, 3, 4, 4L, 5 and 6 genes from Iranian patients with Leber’s hereditary optic neuropathy (LHON)

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Abstract

Leber’s hereditary optic neuropathy (LHON) is an optic nerve dysfunction resulting from mutations in mitochondrial DNA (mtDNA), which is transmitted in a maternal pattern of inheritance. It is caused by three primary point mutations: G11778A, G3460A and T14484C; in the mitochondrial genome. These mutations are sufficient to induce the disease, accounting for the majority of LHON cases, and affect genes that encode for the different subunits of mitochondrial complexes I and III of the mitochondrial respiratory chain. Other mutations are secondary mutations associated with the primary mutations. The purpose of this study was to determine MT-ND variations in Iranian patients with LHON. In order to determine the prevalence and distribution of mitochondrial mutations in the LHON patients, their DNA was studied using PCR and DNA sequencing analysis. Sequencing of MT-ND genes from 35 LHON patients revealed a total of 44 nucleotide variations, in which fifteen novel variations—A14020G, A13663G, C10399T, C4932A, C3893G, C10557A, C12012A, C13934T, G4596A, T12851A, T4539A, T4941A, T13255A, T14353C and del A 4513—were observed in 27 LHON patients. However, eight patients showed no variation in the ND genes. These mutations contribute to the current database of mtDNA polymorphisms in LHON patients and may facilitate the definition of disease-related mutations in human mtDNA. This research may help to understand the disease mechanism and open up new diagnostic opportunities for LHON.

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Acknowledgments

This work was supported by a research grant No. 385, from the National Institute for Genetic Engineering and Biotechnology (NIGEB) of Tehran, Iran.

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Biotechnology, Faculty of Chemistry, University of Kashan, Kashan, Iran

    Zahra Rezvani

  2. Medical Genetics Department, National Institute for Genetic Engineering and Biotechnology, Tehran, Iran

    Elmira Didari & Massoud Houshmand

  3. Medical Genetics Department, Special Medical Center, Tehran, Iran

    Ahoura Arastehkani, Vadieh Ghodsinejad, Omid Aryani & Massoud Houshmand

  4. Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia

    Behnam Kamalidehghan

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  1. Zahra Rezvani
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  2. Elmira Didari
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Correspondence to Massoud Houshmand.

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Rezvani, Z., Didari, E., Arastehkani, A. et al. Fifteen novel mutations in the mitochondrial NADH dehydrogenase subunit 1, 2, 3, 4, 4L, 5 and 6 genes from Iranian patients with Leber’s hereditary optic neuropathy (LHON). Mol Biol Rep 40, 6837–6841 (2013). https://doi.org/10.1007/s11033-013-2801-2

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  • DOI: https://doi.org/10.1007/s11033-013-2801-2

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