J Korean Ophthalmol Soc.  2017 Jan;58(1):117-123. 10.3341/jkos.2017.58.1.117.

A Case of Atypical Leber Hereditary Optic Neuropathy Associated with MT-TL1 Gene Mutation Misdiagnosed with Glaucoma

  • 1Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. htlim@amc.seoul.kr


Leber hereditary optic neuropathy (LHON) is one of the most common hereditary optic neuropathies caused by mutations of mitochondrial DNA. Three common mitochondrial mutations causing LHON are m.3460, m.11778, and m.14484. We report a rare mutation of the mitochondrial tRNA (Leu [UUR]) gene (MT-TL1) (m.3268 A > G) in a patient with bilateral optic atrophy.
A 59-year-old female diagnosed with glaucoma 3 years earlier at a community eye clinic presented to our neuro-ophthalmology clinic. On examination, her best corrected visual acuity was 0.4 in the right eye and 0.7 in the left eye, and optic atrophy was noticed in both eyes. Optical coherence tomography revealed retinal nerve fiber layer (RNFL) thinning in both eyes; average RNFL thickness was 52 µm in the right eye and 44 µm in the left eye, but the papillomacular bundle was relatively preserved in both eyes. Goldmann perimetry demonstrated peripheral visual field defects, mostly involving superotemporal visual field in both eyes. Mitochondrial DNA mutation test showed an unusual mutation in MT-TL1 gene seemingly related to this optic neuropathy.
We found a rare mutation (m.3268 A > G) of the mitochondrial DNA in a patient having bilateral optic atrophy, which led to the diagnosis of LHON. There have been previous reports about mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) and infantile myopathy caused by MT-TL1 mutation, but this is the first case of LHON associated with the same mutation. In this case of LHON associated with MT-TL1 mutation, atypical clinical features were observed with a relatively mild phenotype and peripheral visual field defects.


Glaucoma; Leber hereditary optic neuropathy; MT-TL1; Mutation; Optic atrophy

MeSH Terms

DNA, Mitochondrial
MELAS Syndrome
Middle Aged
Muscular Diseases
Nerve Fibers
Optic Atrophy
Optic Atrophy, Hereditary, Leber*
Optic Nerve Diseases
RNA, Transfer
Tomography, Optical Coherence
Visual Acuity
Visual Field Tests
Visual Fields
DNA, Mitochondrial
RNA, Transfer


  • Figure 1. Fundus photographs (A; the right eye, B; the left eye) of the patient at the initial visit. Optic disc pallor, increased cup/disc ratio, diffuse retinal nerve fiber layer defects, retinal arterial attenuation in both eyes. Note that optic disc pallor is more significant than cupping. Epiretinal membrane in the right eye.

  • Figure 2. Spectral-domain Optical Coherence Tomograph of the patient at the initial visit. Profound thinning of retinal nerve fiber layer in both eyes. Note that the papillomacular bundles are relatively preserved in both eyes. RNFL = retinal nerve fiber layer; ONH = optic nerve head; OD = oculus dexter; OS = oculus sinister; C/D = cup/disc; TEMP = temporal; SUP = superior; NAS = nasal; INF = inferior; S = superior; N = nasal; I = inferior; T = temporal.

  • Figure 3. Goldmann perimetry of the patient at the initial visit. Peripheral visual field defects, mostly superotemporal visual field de-fects were seen in both eyes. Central vision was not severely impaired as the papillomacular bundle was preserved. OD = oculus dexter; OS = oculus sinister.

  • Figure 4. Mutation chromatogram of the patient. A mutation of MT-TL1; m.3268 A>G homoplasmy mutation. The 37th nucleotide A of MT-TL1 gene was substituted by G. The muta-tion was located at the anticodon loop of tRNA-Leu.



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