Abstract

Introduction: Leber Hereditary Optic Neuropathy (LHON) is a rare disease with bilateral optic atrophy, the main cause is mitochondrial genetic mutations associated with dysfunction of the complex I mitochondrial electron transport chain. This study is conducted to determine the spectrum of new mutations in seven subunits of the mitochondrial complex I. Methodology: The subunit genes of the mitochondrial complex I of 47 Iranian leber patients were sequenced and analyzed with the Sanger method. Discussion and Results: LHON’s unique maternally inherited trait, linked to mitochondrial DNA (mtDNA) point mutations, impacts complex I subunit genes, particularly m.G11778A MTND4, m.G3460A MT-ND1, and m.T14484C MT-ND6 mutations in about 90% of cases. But we found new mutations other than primary mutations that could be important. New variants have been found in the mitochondrial complex I subunit, the frequency of these changes in ND1, ND4, ND5, and ND6 genes were equal to 17%, 12%, 34%, and 37%, respectively. The lately found m.A11775G MTND4 gene with 0.2% of allelic frequency in 2 patients, m.C13540G MTND5 with an allelic frequency of 0.07%in 1 patient, m.T14441A MTND6 with 0.3% of allelic frequency in 4 patients, m.T14503A MTND6 with 0.3% of allelic frequency in 4 patients, and m.A14496T MTND6 with 0.07% of allelic in 1 patient frequency have been reported. The mentioned findings demonstrated the existence of previously unknown mutations associated with LHON, highlighting the importance of ongoing mutation screening to increase our understanding of the genetic variation associated with this disease.