The Pathological Mechanisms and Novel Therapeutics for Leber’s Hereditary Optic Neuropathy
Optic neuropathies were estimated to affect 115 in 100,000 population in 2018. Leber’s Hereditary Optic Neuropathy (LHON) as one of such optic neuropathy diseases that was first identified in 1871 and can be defined as a hereditary mitochondrial disease. LHON is associated with three mtDNA point mutations which are G11778A, T14484, and G3460A that affect the NADH dehydrogenase subunits of 4, 6, and 1, respectively. However, in most cases, only one point mutation is involved. Generally, in…
A Rare ND5 Mutation Causing Leber’s Hereditary Optic Neuropathy
Mutations to the ND5 gene are uncommonly associated with Leber’s hereditary optic neuropathy (LHON). Herein, we describe a 57-year-old man with the m. 13528A>G, p. (Thr398Ala) mutation at the ND5 gene who presented with progressive bilateral vision loss over the course of 3 months. He had a significant history of smoking and alcohol consumption. Visual field testing demonstrated bilateral central scotomas. At 2-year follow-up, his visual acuity improved relative to baseline and temporal optic…
Genetic Aberration Analysis of Mitochondrial Respiratory Complex I Implications in the Development of Neurological Disorders and Their Clinical Significance
Growing neurological diseases pose difficult challenges for modern medicine to diagnose and manage them effectively. Many neurological disorders mainly occur due to genetic alteration in genes encoding mitochondrial proteins. Moreover, mitochondrial genes exhibit a higher rate of mutation due to the generation of Reactive oxygen species (ROS) during oxidative phosphorylation operating in their vicinity. Among the different complexes of Electron transport chain (ETC), NADH: Ubiquinone…
Clinical expression and mitochondrial deoxyribonucleic acid study in twins with 14484 Leber’s hereditary optic neuropathy: A case report
CONCLUSION: This 11-year follow-up of monozygotic twins showed additional genetic modifications and epigenetic factors are possibly associated with discordance for LHON.
Leber Hereditary Optic Neuropathy (LHON)
Leber hereditary optic neuropathy (LHON) is a rare mitochondrial disorder that typically presents in young males with sequential visual loss due to optic neuropathy.
Modeling Reactive Oxygen Species-Induced Axonal Loss in Leber Hereditary Optic Neuropathy
Leber hereditary optic neuropathy (LHON) is a rare syndrome that results in vision loss. A necessary but not sufficient condition for its onset is the existence of known mitochondrial DNA mutations that affect complex I biomolecular structure. Cybrids with LHON mutations generate higher rates of reactive oxygen species (ROS). This study models how ROS, particularly H(2)O(2), could signal and execute the axonal degeneration process that underlies LHON. We modeled and explored several hypotheses…
Leber’s hereditary optic neuropathy clinical features in patients with mitochondrial DNA m.13513G>A candidate mutation
CONCLUSION: The m.13513G>A mutation can be considered as primary LHON mutation. The list of pathogenic variants recommended for testing LHON can include this mutation. The m.13513 G>A mutation determines the mild LHON course and good visual functions prognosis in these patients.
Candidate Modifier Genes for the Penetrance of Leber’s Hereditary Optic Neuropathy
Leber’s hereditary optic neuropathy (LHON) is a maternally transmitted disease caused by mitochondria DNA (mtDNA) mutation. It is characterized by acute and subacute visual loss predominantly affecting young men. The mtDNA mutation is transmitted to all maternal lineages. However, only approximately 50% of men and 10% of women harboring a pathogenic mtDNA mutation develop optic neuropathy, reflecting both the incomplete penetrance and its unexplained male prevalence, where over 80% of patients…
Leber’s Hereditary Optic Neuropathy and Hypertrophic Cardiomyopathy
Leber’s hereditary optic neuropathy (LHON) is a mitochondrial condition that gradually affects the central vision. In the current case report, we present 2 relatives with LHON due to a pathogenic variant within ND1 with a clinical phenotype resembling hypertrophic cardiomyopathy, including a short PQ-interval and hypertrophy on electrocardiogram as well as severe hypertrophy of the left ventricle on echocardiography. These findings highlight the importance of offering routine cardiac…
Relative Leukocyte Telomere Length and Telomerase Complex Regulatory Markers Association with Leber’s Hereditary Optic Neuropathy
Background and Objectives: To evaluate the association of relative leukocyte telomere length (RLTL) and telomerase complex regulatory markers with Leber’s hereditary optic neuropathy (LHON). Material and Methods: A case-control study was performed in patients with LHON (≥18 years) and healthy subjects. The diagnosis of LHON was based on a genetic blood test (next-generation sequencing with Illumina MiSeq, computer analysis: BWA2.1 Illumina BaseSpace, Alamut, and mtDNA Variant analyzer 1000 were…