Hereditary Optic Neuropathy Associated with a Novel MT-RNR1 Mutation: A Case Report

Hereditary optic neuropathies are mitochondrial disorders characterized by retinal ganglion cell degeneration and optic nerve dysfunction. Variants in MT-RNR1, a gene classically associated with aminoglycoside-induced and nonsyndromic sensorineural hearing loss, are increasingly recognized in hereditary optic neuropathy. We report the first case of hereditary optic neuropathy associated with the novel MT-RNR1 m.960delC variant, expanding the known genetic spectrum of this emerging mitochondrial optic neuropathy phenotype.

A 61-year-old woman presented with bilateral optic neuropathy characterized by optic disc pallor out of proportion to cupping, diffuse retinal nerve fiber layer and ganglion cell layer thinning, and bilateral visual field abnormalities. Best-corrected visual acuity was 20/30 in the right eye and 20/20 in the left eye, with intraocular pressures within the normal range. Gonioscopy demonstrated open angles bilaterally. Visual field testing demonstrated nonglaucomatous defects, and laboratory investigations were unremarkable. MRI of the orbits and brain with gadolinium was normal. Mitochondrial genetic testing identified the novel MT-RNR1 m.960delC variant at 87.2% heteroplasmy. The overall phenotype was consistent with hereditary optic neuropathy associated with mitochondrial dysfunction.

This case expands the spectrum of MT-RNR1-associated hereditary optic neuropathy through identification of the novel m.960delC variant. The proximity of m.960delC to the previously reported m.956delC variant raises the possibility of a functionally important region within MT-RNR1. These findings further support MT-RNR1 as an emerging candidate gene in hereditary optic neuropathy, with important implications for genetic testing and disease recognition.