![]() Injury of retinal neurons and degeneration of the optic nerve lead to the specific features of LHON. Missense mutations in mtDNA genes associated with LHON cause mitochondrial dysfunction with drastic defects in complex I, the largest complex in the OXPHOS, leading to increased reactive oxygen species (ROS) and a marked reduction in the ATP supply of the retina. Mitochondria have their own DNA (mtDNA) that encode several subunits of large enzyme complexes in the mitochondria oxidative phosphorylation pathway system (OXPHOS), which takes place in the inner membrane of mitochondria that catalyze ATP synthesis and provide cellular energy. Now, it is explained as a non-Mendelian genetic pattern of mitochondrial inheritance. LHON was first revealed in 1871 by a German ophthalmologist, Theodor Leber, who first described the maternal transmission of the disorder. Leber’s hereditary optic neuropathy (LHON OMIM 535000), is a neurodegenerative inherited form of painless loss of central vision in both eyes, which may happen simultaneously or sequentially. Our results support the need for further studies of genetic background and its role in the penetrance and severity of LHON. MITOMASTER analysis showed that the two well-known primary mutations belong to the R haplogroup, while the rare LHON m.8836A>G was detected within the N1b haplogroup. Various secondary mutations were detected in association with the primary mutations. Our study revealed two well-known primary LHON mutations, m.11778G>A and m.3460G>A, and one rare LHON mutation, m.8836A>G. Mitochondrial haplogroup analysis was performed by MITOMASTER. ![]() All obtained sequence variants were compared to human mtDNA databases, and their potential pathogenic characteristics were assessed by bioinformatics tools. This study is based on a mutational screening of entire mtDNA in eight Serbian probands clinically and genetically diagnosed with LHON and four of their family members, who are asymptomatic mutation carriers. Leber’s hereditary optic neuropathy (LHON) is a maternally inherited disorder that affects central vision in young adults and is typically associated with mitochondrial DNA (mtDNA) mutations.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |