Mitochondrial retinal dystrophy associated with the m.3243A>G mutation

Ophthalmology. 2013 Dec;120(12):2684-2696. doi: 10.1016/j.ophtha.2013.05.013. Epub 2013 Jun 24.


Objective: To describe the spectrum of retinal abnormalities associated with the m.3243A>G mutation in the mitochondrial MTTL1 gene and to analyze putative correlations among the severity of retinal abnormalities, disease severity in other organ systems, and heteroplasmy levels.

Design: Observational, cohort-based, cross-sectional study.

Participants: Twenty-nine patients carrying the m.3243A>G mutation.

Methods: Extensive clinical examinations, including visual acuity testing, indirect ophthalmoscopy, color fundus photography, fundus autofluorescence (FAF), high-resolution optical coherence tomography (OCT), and central visual field analysis. In selected patients, Goldmann perimetry, fluorescein angiography, full-field electroretinography (ERG) and electro-oculography (EOG), and color vision testing were performed. Heteroplasmy levels of the m.3243A>G mutation were measured in leukocytes, urinary epithelial cells (UECs), and buccal mucosa. The Newcastle Mitochondrial Disease Adult Scale (NMDAS) score was measured for all patients.

Main outcome measures: Age at onset, visual acuity, fundus appearance, FAF, OCT findings, systemic disease features, heteroplasmy levels, and NMDAS scores.

Results: Twenty-five of the 29 mutation carriers (86%) had retinal abnormalities that could be classified into 4 grades. Six patients (21%) had grade 1 retinal dystrophy with fine pigment abnormalities that were clearly visible with FAF and fluorescein angiography. Eleven patients (38%) had grade 2 abnormalities that were characterized by yellowish or mildly pigmented deposits in the early stage; in advanced grade 2, these pigment changes encompassed the entire macula and often encircled the optic disc. Six patients (21%) had grade 3 disease in which profound chorioretinal atrophy was present outside the fovea. Two patients (7%) with retinal abnormalities had grade 4 disease, in which the fovea was affected by atrophy, with marked loss of visual acuity. The grade of mitochondrial retinal dystrophy correlated significantly with both age (r = -0.483, P = 0.008) and visual acuity (r = -0.614, P < 0.001), whereas no correlation was observed with heteroplasmy level or overall disease involvement.

Conclusions: Mitochondrial retinal dystrophy associated with the m.3243A>G mutation has specific characteristics that can be classified into 4 grades based on the findings on ophthalmoscopy, FAF, and OCT. However, because the maternal inheritance pattern can be masked and the systemic disease associations can be variable or even absent, the disease may be misdiagnosed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cohort Studies
  • Cross-Sectional Studies
  • DNA Mutational Analysis
  • DNA, Mitochondrial / genetics*
  • Electrooculography
  • Electroretinography
  • Female
  • Fluorescein Angiography
  • Heterozygote
  • Humans
  • Male
  • Middle Aged
  • Mitochondrial Diseases / classification*
  • Mitochondrial Diseases / diagnosis
  • Mitochondrial Diseases / genetics*
  • Ophthalmoscopy
  • Point Mutation*
  • RNA, Transfer, Leu / genetics*
  • Retinal Dystrophies / classification*
  • Retinal Dystrophies / diagnosis
  • Retinal Dystrophies / genetics*
  • Tomography, Optical Coherence
  • Visual Acuity
  • Young Adult


  • DNA, Mitochondrial
  • RNA, Transfer, Leu