Letter to the Editor: Variable response to Idebenone in LHON is multifactorial
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PhNR and Peripapillary RNFL Changes in Leber Hereditary Optic Neuropathy With m.G11778A Mutation
CONCLUSION: In the subacute phase, the function of RGCs was severely impaired. Thickness of pRNFL decreased significantly in four quadrants during disease progression. In the chronic phase, pRNFL thickness decreased slightly. Carriers have shown RGCs dysfunction before pathological changes occur, suggesting subclinical abnormalities.
Ischemic optic neuropathy as first presentation in patient with m.3243 A > G MELAS classic mutation
CONCLUSIONS: Atypical clinical presentations must be always considered in mitochondrial disorders, even in well-described phenotypes and when mutational load in peripheral tissue is low. Mitotic segregation of mitochondrial DNA (mtDNA) does not allow to know the exact degree of heteroplasmy existent within different tissue, such as retina and optic nerve. Important therapeutic implications arise from a correct diagnosis of atypical presentation of mitochondrial disorders.
Probing the pathogenicity of patient-derived variants of MT-ATP6 in yeast
The list of mitochondrial DNA (mtDNA) variants detected in individuals with neurodegenerative diseases is constantly growing. Evaluating their functional consequences and pathogenicity is not easy, especially when they are found in only a limited number of patients together with wild-type mtDNA (heteroplasmy). Owing to its amenability to mitochondrial genetic transformation and incapacity to stably maintain heteroplasmy, and the strong evolutionary conservation of the proteins encoded in…
Autosomal recessive Leber hereditary optic neuropathy, a new neuro-ophthalmo-genetic paradigm
Leber Hereditary Optic Neuropathy (LHON) is a primary inherited neurodegenerative disorder of the optic nerve. It has been ascribed to variants in the mitochondrial genome, mainly the m.3460G > A, m.11778G > A and m.14484T > C mutations in ND1, ND4 and ND6 respectively. Nonetheless, inconclusive molecular diagnosis is not uncommon. Recently, biallelic mutations in the NDUFS2, DNAJC30, MCAT and NDUFA12 nuclear genes have been identified in unresolved LHON cases, identifying an autosomal recessive…
Comparison of different gene-therapy methods to treat Leber hereditary optic neuropathy in a mouse model
CONCLUSIONS: These results in a pre-clinical mouse model of LHON suggest that mitochondrially-targeted AAV gene therapy, compared to allotopic AAV gene therapy, is more efficient in rescuing the LHON phenotype.
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.