First Case in Lithuania of an Autosomal Recessive Mutation in the DNAJC30 Gene as a Cause of Leber’s Hereditary Optic Neuropathy
CONCLUSION: This case highlights the importance of considering arLHON as a possible diagnosis for patients with optic neuropathy, because the phenotype of arLHON appears to be identical to that of mtLHON and cannot be distinguished by clinicians.
Age-Associated Differences in Optic Disc Findings of Leber’s Hereditary Optic Neuropathy
We aimed to investigate the relationship between age and acute-phase optic disc findings in Leber’s Hereditary Optic Neuropathy (LHON). We examined 27 LHON patients (27 eyes) with the m.11778 G>A mutation within two months of onset, with acute-phase optic disc findings. We analyzed the relationship between age and three key optic disc features: peripapillary telangiectasia, disc hyperemia, and retinal nerve fiber layer (RNFL) swelling. The median age of onset was 37 years (range: 10-68), with 22…
A Case of Late-Onset Leber’s Hereditary Optic Neuropathy in Association with Heteroplasmic m.11778G>A/ND4 Mutation
A 68-year-old man described a progressive, painless, and bilateral reduction of visual acuity, with greater difficulties in central vision, over a period of 3 years. His past medical history was unremarkable, and he admitted a long exposure to tobacco smoking and moderate daily alcohol intake. The first ophthalmological evaluation confirmed a bilateral reduction of visual acuity, without other major findings. Visual fields showed a central scotoma in the right eye and a temporal…
Whole mitochondrial genome sequencing in individuals with Leber hereditary optic neuropathy negative for the common pathogenic mitochondrial DNA variants
CONCLUSION: Our study of a well-characterized Indian LHON cohort uncovered rare mtDNA variants that should be considered when assessing undiagnosed optic neuropathy cases. Additionally, it underscores the effectiveness of NGS in identifying heteroplasmic mtDNA variants. This indicates that whole mitochondrial genome sequencing via NGS is a more efficient and preferred approach for routine molecular genetic testing.
Rasch analysis of the NEI-VFQ-25: vision-related quality of life in Leber hereditary optic neuropathy after lenadogene nolparvovec gene therapy
CONCLUSIONS: The scoring structure of the original NEI-VFQ-25 has limitations that undermine its psychometric validity as a measure of VRQoL. Using the Rasch-revised NEI-VFQ-25, we determined that improvement in VRQoL after treatment with lenadogene nolparvovec was driven predominantly by an improvement in socioemotional functioning.
Outcomes of idebenone therapy for Leber hereditary optic neuropathy in a cohort of patients from Wales
CONCLUSION: The present cohort demonstrates evidence of CRR in a high proportion of patients reaching 27 months of treatment. Further follow-up and a larger cohort of patients will provide further insight into the real-world efficacy of idebenone in LHON.
Structural insights into DdCBE in action enable high-precision mitochondrial DNA editing
DddA-derived cytosine base editor (DdCBE) couples transcription activator-like effector (TALE) arrays and the double-stranded DNA (dsDNA)-specific cytidine deaminase DddA to target mitochondrial DNA (mtDNA) for editing. However, structures of DdCBE in action are unavailable, impeding its mechanistic-based optimization for high-precision-demanding therapeutic applications. Here, we determined the cryo-electron microscopy (cryo-EM) structures of DdCBE targeting two native mitochondrial gene loci…
Estradiol alleviates disease phenotypes caused by m.3635G > a mutations by activating mitochondrial biogenesis and PINK1-Parkin mediated mitophagy in iPSC-derived retinal pigment epithelium cells
Leber’s hereditary optic neuropathy (LHON), a mitochondrial disorder marked by central vision loss, exhibits incomplete penetrance and male predominance. Since there are no adequate models for understanding the rapid vision loss associated with LHON, we generated induced pluripotent stem cells (iPSCs) from LHON patients carrying the pathogenic m.3635G > A mutation and differentiated them into retinal pigment epithelium (RPE) cells. The mutation disrupted mitochondrial dynamics, suppressing…
MetabOCT: a clinical trial looking for a metabolomic signature predicting the onset of Leber’s hereditary optic neuropathy in healthy MtDNA mutations carriers
CONCLUSION: Identifying pre-clinical biomarkers would open a window for clinical trials.
Quantitative assessment of retinal microvasculature using optical coherence tomography angiography and correlation with visual acuity in leber’s hereditary optic neuropathy
CONCLUSION: LHON is characterized by diffuse impairment of the retinal microvasculature, predominantly affecting the macular region and corresponding to the papillomacular bundle. Furthermore, BCVA demonstrated significant correlations with retinal blood flow and structural parameters.