Novel Variants in Mitochondrial Ribosomal RNA Genes MT-RNR1 and MT-RNR2 Identified In Hereditary Optic Neuropathy Initially Presenting as Normal Tension Glaucoma: A Case Report

Introduction: Hereditary optic neuropathy may be caused by various mitochondrial or nuclear DNA mutations affecting the mitochondrial function. A growing body of evidence shows that mutations in nonclassical mitochondrial genes, including the ribosomal RNA genes MT-RNR1 and MT-RNR2, have been reported in patients with hereditary optic neuropathy, although their pathogenicity remains uncertain. Herein, we report a case initially diagnosed as normal tension glaucoma in which whole mtDNA sequencing identified two novel variants in MT-RNR1 and MT-RNR2. Case Presentation: A 36-year-old man was referred for glaucoma assessment but was found to have bilateral symmetric temporal optic disc pallor and retinal nerve fibre layer (RNFL) thinning that was inconsistent with a glaucomatous pattern. Intraocular pressure (IOP), Humphrey visual fields, colour vision, and pupillary responses were normal. Genetic testing was negative for the three primary Leber’s Hereditary Optic Neuropathy (LHON) mutations, but identified MT-RNR1:m.990T>C and MT-RNR2:m.2619A>G, both at 99.5% heteroplasmy and classified as ACMG Class 3. Visual function remained stable at six-month follow-up. Conclusion: Neither MT-RNR1 and MT-RNR2 variants could be definitively linked to the hereditary optic neuropathy in this patient, and they are best regarded as findings of uncertain significance. This case highlights a diagnostic pitfall as non-glaucomatous optic disc pallor can be mistaken for normal tension glaucoma, and underscores the diagnostic value of whole mtDNA sequencing when primary LHON screening is negative.