Exploring the Phenotypic Heterogeneity and Bioenergetic Profile of the m.13513G>A mtDNA Substitution: A Heteroplasmy Perspective
The m.13513G>A (p.Asp393Asn) substitution in the MT-ND5 (Mitochondrially Encoded NADH/Ubiquinone Oxidoreductase Core Subunit 5) gene is a common pathogenic variant associated with primary mitochondrial disorders. It frequently causes Leigh syndrome and mitochondrial encephalomyopathy with lactate acidosis and stroke-like episodes (MELAS). In this study, we present clinical data, heteroplasmy levels in various tissues (blood, urine, and skin fibroblasts), and bioenergetic characteristics from a…
Literature Commentary
In this issue of JNO, Drs. Mark L. Moster, Marc J. Dinkin, and Deborah I. Friedman discuss the following 6 articles:Piehl F, Eriksson-Dufva A, Budzianowska A, Feresiadou A, Hansson W, Hietala MA, Håkansson I, Johansson R, Jons D, Kmezic I, Lindberg C, Lindh J, Lundin F, Nygren I, Punga AR, Press R, Samuelsson K, Sundström P, Wickberg O, Brauner S, Frisell T. Efficacy and safety of rituximab for new-onset generalized myasthenia gravis: the RINOMAX randomized clinical trial. JAMA Neurol….
The crossroads of Leber hereditary optic neuropathy and autosomal dominant optic Atrophy: Clinical profiles of patients with coexisting pathogenic genetic variants
CONCLUSION AND IMPORTANCE: Mitochondrial optic neuropathies, which result in loss of retinal ganglion cells, are a substantial cause of visual impairment. Herein, we report two cases of combined LHON- and ADOA-causing pathogenic variants in two brothers, in addition to the genetic and ophthalmologic profile of their parents and two sisters.
A viewpoint about Lenadogene nolparvovec failing to meet its primary endpoint even though it permanently corrects the m.11778G>A mutation causative of LHON
No abstract
Bezafibrate was unsuccessful to treat leber hereditary optic neuropathy
No abstract
Mechanism of BNIP3-mediated mitophagy in m.3635G>A related Leber hereditary optic neuropathy
CONCLUSION: The m.3635G>A inhibits BNIP3-mediated mitophagy, thereby contributing to the pathogenesis of LHON.
Modifier variants in metabolic pathways are associated with an increased penetrance of Leber’s Hereditary Optic Neuropathy
Leber’s hereditary optic neuropathy (LHON) is a debilitating mitochondrial disease characterised by bilateral painless vision loss. Despite being the most prevalent mitochondrial disorder, the precise pathophysiological mechanisms underlying the penetrance of LHON remain poorly understood. Nuclear modifier genes have been long suspected to affect phenotype-severity, however, specific cellular pathways implicated in the disease penetrance have been only suggested recently. In recent years,…
Recurrent Optic Neuritis as a Misleading Presentation of Leber Hereditary Optic Neuropathy: The Need for High Clinical Suspicion in Young Men
A 29-year-old Chinese gentleman presented with acute-onset right eye (RE) central scotoma and blurring of vision. Upon presentation, RE visual acuity (VA) was 6/30. The RE optic disc (OD) was mildly swollen, but other findings were unremarkable. A computed tomography (CT) imaging study showed no evidence of a space-occupying lesion. The erythrocyte sedimentation rate (ESR) and other laboratory blood results were normal. The patient was empirically treated with a course of steroids for optic…
Leber hereditary optic neuropathy: utilities and carer burden from British and Irish participants
CONCLUSIONS: Findings suggest the HUI-3 may be more sensitive to the HRQL impact of vision loss compared to the EQ-5D and TTO method. The data indicate the potential value of an effective treatment for LHON. Qualitative findings describe the impact of LHON on carers. However, the burden described in the qualitative data was incongruent with quantitative measures, particularly the EQ-5D-5L. This demonstrates the value of conducting mixed-methods research and the importance of selecting measures…
Isolated and Syndromic Genetic Optic Neuropathies: A Review of Genetic and Phenotypic Heterogeneity
Nonsyndromic and syndromic hereditary optic neuropathies (HONs) encompass a variety of genetic illnesses that cause progressive optic nerve damage, resulting in considerable vision impairment. These disorders result from pathogenic variants in mitochondrial or nuclear DNA, impacting essential cellular processes like oxidative phosphorylation, mitochondrial dynamics, and neuroprotection. Advances in next-generation sequencing (NGS) have significantly improved the identification of genetic…