LHON Plus Due to the Variant m.3460G > A Requires Extensive Investigation and Close Monitoring
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Optic Nerve Structural and Functional Changes in LHON-Affected and Asymptomatic Maternal Relatives: Association with H and HV Mitochondrial Haplogroups
Leber Hereditary Optic Neuropathy (LHON) affects a minority of carriers of causative mitochondrial DNA mutations. We investigated a cohort of patients with LHON, including m.11778G>A, m.3460G>A, m.14484T>C and DNAJC30 c.152A>G variants, and their asymptomatic maternal carrier relatives for additional potential associations with vision loss. We assessed visual acuity, optical coherence tomography (OCT) of the peripapillary retinal nerve fibre layer (RNFL), visually evoked potential…
Psychometric Validity of the Visual Function Index in Leber Hereditary Optic Neuropathy
CONCLUSIONS: Clinicians and researchers using the VF-14 with LHON patients should be aware of its limitations. Compared to the original version, the proposed Rasch-based structure of the VF-14R appears to offer improved psychometric performance and interpretation of vision-related activity limitation.
Nuclear modifier YARS2 allele correction restored retinal ganglion cells-specific deficiencies in Leber’s hereditary optic neuropathy
Leber’s hereditary optic neuropathy (LHON) is a maternally transmitted eye disease due to the degeneration of retinal ganglion cells (RGC). Mitochondrial 11778G > A mutation is the most common LHON-associated mitochondrial DNA (mtDNA) mutation. Our recent studies demonstrated some LHON families manifested by synergic interaction between m.11778G > A mutation and YARS2 allele (c.572G > T, p.Gly191Val) encoding mitochondrial tyrosyl-tRNA synthetase. However, the RGC-specific effects of…
Clinical Profile of Patients with Leber Hereditary Optic Neuropathy (LHON): An Ambispective Study of North Indian Cohorts
BACKGROUND: Leber hereditary optic neuropathy (LHON) is a maternally inherited disease resulting in irreversible visual loss usually in patients belonging to the age group of 15-35 years. Clinically, the patients present with sequential or bilateral, painless, progressive visual loss with central (or ceco-central) scotomas. Although the three mutations, namely, G11778A, T14484C, and G3460A contribute to >95% of LHON cases globally, the relative frequency of each mutation varies.
Is the disease risk and penetrance in Leber hereditary optic neuropathy actually low?
Pedigree analysis showed that a large proportion of Leber hereditary optic neuropathy (LHON) family members who carry a mitochondrial risk variant never lose vision. Mitochondrial haplotype appears to be a major factor influencing the risk of vision loss from LHON. Mitochondrial variants, including m.14484T>C and m.11778G>A, have been added to gene arrays, and thus many patients and research participants are tested for LHON mutations. Analysis of the UK Biobank and Australian cohort studies…
Low disease risk and penetrance in Leber hereditary optic neuropathy
The risk of Leber hereditary optic neuropathy (LHON) has largely been extrapolated from disease cohorts, which underestimate the population prevalence of pathogenic primary LHON variants as a result of incomplete disease penetrance. Understanding the true population prevalence of primary LHON variants, alongside the rate of clinical disease, provides a better understanding of disease risk and variant penetrance. We identified pathogenic primary LHON variants in whole-genome sequencing data of a…
Adeno-associated virus mediated gene therapy for neuroprotection of retinal ganglion cells in glaucoma
Glaucoma is a group of diseases typically characterized by the degeneration of the optic nerve and is one of the world’s leading causes of blindness. Although there is no cure for glaucoma, reducing intraocular pressure is an approved treatment to delay optic nerve degeneration and retinal ganglion cell (RGC) death in most patients. Recent clinical trials have evaluated the safety and efficacy of gene therapy vectors for the treatment of inherited retinal degenerations (IRDs), and the results…
Choroidal vascularity index in hereditary optic neuropathies
CONCLUSION: CVI is preserved in DOA and LHON patients, suggesting that even in the chronic phase of the neuropathy the choroidal structure is not irreversibly compromised.
Leber’s Hereditary Optic Neuropathy with Mitochondrial DNA Mutation G11778A: A Systematic Literature Review and Meta-Analysis
CONCLUSIONS: The G11778A mutation is a prevalent mitochondrial DNA mutation accounting for over half of LHON cases with three primary mutations. Spontaneous visual recovery is rare, and no effective treatment is currently available.