Leber Hereditary Optic Neuropathy Caused by the Rare MT-ND1 m.3394T>C Mutation: A Case With Favorable Visual Prognosis and a Literature Review
Leber hereditary optic neuropathy (LHON) is an inherited mitochondrial optic neuropathy characterized by acute or subacute painless central visual loss. Most cases are associated with three primary mitochondrial DNA mutations; however, rare variants remain incompletely characterized. Early diagnosis is essential for appropriate management and genetic counseling. We report the case of a 51-year-old Lithuanian woman who presented with painless, progressive central visual loss. Initial neurological…
A Heteroplasmic MT-CO2 m.8024G > A Variant Is Associated with Mitochondrial Bioenergetic Deficiency and Optic Atrophy
Leber’s hereditary optic neuropathy (LHON) is a hereditary neurodegenerative disorder caused by pathogenic mitochondrial DNA (mtDNA) variants. While MT-CO2 defects are implicated in neurodegeneration, their direct association with optic atrophy has not been reported. We identify a heteroplasmic MT-CO2 variant, m.8024G > A (p.Glu147Lys), in a patient with progressive optic atrophy and explore its potential association with mitochondrial dysfunction. A 13-year-old male with progressive…
Mesenchymal stem cell mitochondrial transfer effectively protects Leber’s Hereditary Optic Neuropathy (LHON) mutant cells from mitochondrial damage
Leber’s Hereditary Optic Neuropathy (LHON) is the most prevalent mitochondrial inherited disorder, primarily caused by primary mitochondrial mutations. Clinically, LHON is characterized by degeneration of optic nerves that leads to acute or subacute sudden or painless central vision loss. Currently no effective treatment has been established for LHON. Recent studies have highlighted the significance of intercellular mitochondrial transfer, which facilitates communication between cells and…
Diagnostic and Imaging Features of Leber Hereditary Optic Neuropathy: An Individual Participant Data Meta-Analysis
CONCLUSION: In this IPDMA, patients of all ages, both male and female, presented with vision loss from LHON. There was a propensity for T2 -hyperintensity of the optic nerves and/or chiasm, particularly in females, and associated post-contrast enhancement of the lesions. Given the profound impact early diagnosis can make on saving patients’ vision, it is important for radiologists to understand neuroimaging and clinical associations of LHON.
Progressive generalized dystonia caused by a mutation in the MT-ND6 gene
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Optic neuropathy arising from the synergy between YARS2 and mitochondrial COX1 mutations
Leber hereditary optic neuropathy (LHON) is a paradigm for mitochondrial retinopathy. Here, we investigate the mechanism underlying the interaction between nuclear modifier and mtDNA mutation(s) that manifests optic neuropathy in vivo to develop an effective therapeutic approach for this disease using mouse models bearing LHON-linked Yars2^(G186V) or COI^(V421A) mutation alone and double mutations. Yars2^(G186V) alters mitochondrial translation and assembly and activities of complex I, III, and…
Molecular Mechanism of Mitochondrial Complex I Disruption by m.14484T>C Underlying Leber Hereditary Optic Neuropathy
Leber’s Hereditary Optic Neuropathy (LHON) is a rare genetic condition and severe neurological disorder characterized by dysfunctional mitochondria under extreme oxidative stress, resulting in retinal ganglion cell death and subsequent rapid bilateral loss of central vision. The m.14484T>C mutation in the ND6 subunit of mitochondrial complex I is known for inducing LHON, and is a prevalent LHON-associated mutation, yet its mechanism of impairment at the molecular level is currently unresolved….
Pharmacological Depletion of Retinal Mononuclear Phagocytes Is Neuroprotective in a Mouse Model of Mitochondrial Optic Neuropathy
CONCLUSIONS: Pexidartinib effectively depletes retinal MNPs and is neuroprotective in the setting of severe RGC mitochondrial dysfunction. This therapeutic effect is additive to that of hypoxia. Combating retinal neuro-inflammation may therefore be a useful adjunct therapy in mitochondrial optic neuropathies like Leber hereditary optic neuropathy (LHON).
Oxidative Stress and Inflammatory Biomarkers in Aqueous Humor and Blood of Patients with Leber’s Hereditary Optic Neuropathy
Leber’s hereditary optic neuropathy (LHON) is a mitochondrial disorder that causes visual impairment due to the degeneration of retinal ganglion cells. Oxidative stress (OS) and inflammatory cytokines have been implicated in its pathophysiology. We investigated, for the first time, the presence of OS biomarkers and inflammatory cytokines in the aqueous humor and peripheral blood of LHON patients compared to controls, aiming to identify potential clinical biomarkers for diagnosis and disease…
Leber Hereditary Optic Neuropathy-Associated Novel Mutation in MT-RNR2 Gene: A Case Report
CONCLUSION: MT-RNR2 gene mutation was the possible cause for LHON in this patient. Herein, we describe a novel mutation and associated clinical features. This case report also underscores the importance of considering LHON as a differential diagnosis for optic neuritis, even in a patient with an established MS.