Supplementary Material for: Two Novel Variants in MT-RNR1 Gene Associated with Hereditary Optic Neuropathy: A Case Report

Abstract Background: Hereditary optic neuropathies are primarily disorders of mitochondrial dysfunction leading to the metabolic failure of the highly energy-dependant retinal ganglion cells. Beyond the canonical variants found in OPA1 or the mitochondrial genome, a growing subset of patients exhibit progressive optic atrophy of unknown origin. Identifying these variants is critical, as they might lead to a diagnostic delay. We report two cases with a previously unreported MT-RNR1 variants, potentially contributing to a hereditary optic neuropathy. Case presentation: A 55-year-old woman with painless progressive optic neuropathy presented with bilateral central scotomas and temporal optic disc pallor. Nutritional, inflammatory, and demyelinating causes were excluded. Genetic testing revealed MT-RNR1:m.1019A>G variant, potentially contributing to a hereditary optic neuropathy. A 59-year-old woman with similar bilateral temporal pallor and symmetric retinal nerve fiber layer thinning was found to harbor MT-RNR1:m.1183T>C variant. Conclusion: MT-RNR1 gene variant was the possible cause of vision loss in these patients with mild vision loss and a clinical picture consistent with a hereditary optic neuropathy. Herein, we describe two novel variants and associated clinical features. This case report introduces a previously unrecognized genetic variant, potentially contributing to a hereditary optic neuropathy.