Retinal dystrophy associated with a single-base deletion mutation in mitochondrial DNA 3271 in patient with MELAS syndrome

  • Kenji OzawaEmail author
  • Kiyofumi Mochizuki
  • Yusuke Manabe
  • Nobuaki Yoshikura
  • Takayoshi Shimohata
  • Ichizo Nishino
  • Yu-ichi Goto
Clinical Case Report



Mitochondrial encephalopathy with lactic acid and stroke-like episodes (MELAS) is caused by mutations in the mitochondrial DNA. Approximately 80% of MELAS patients have an A > G transition mutation at nucleotide pair 3243 in the mitochondrial DNA, m.3243A > G. There are also MELAS patients with a one-base deletion at nucleotide pair 3271 in the mitochondrial DNA, m.3271delT, but these cases are very rare. We report a case of MELAS with the m.3271delT and describe the retinal structure and electrophysiological alterations.


The retinal structure and function of a 37-year-old woman who was referred to our clinic for of nyctalopia were studied. Standard ophthalmological examinations including the medical history, measurements of the best-corrected visual acuity, intraocular pressures, and slit-lamp biomicroscopy, ophthalmoscopy, fluorescein angiography, fundus autofluorescence, spectral-domain optical coherence tomography (SD-OCT), full-field electroretinography (ERG), and multifocal electroretinography (mfERG) were performed.


Fundus examination showed bilateral hypopigmentary changes of the retinal pigment epithelium which extended from the posterior pole to the equator. Fluorescein angiography showed patchy hyperfluorescence due to window defects at the atrophic areas. Fundus autofluorescence demonstrated mild hyperfluorescent lesions in both eyes. SD-OCT showed that the interdigitation zone was indistinct in both eyes, and the inner nuclear layer was slightly thinner. The amplitudes of the rod, cone, and 30-Hz flicker ERGs were severely reduced, and the implicit times were prolonged. The a- and b-waves of the bright-flash mixed rod–cone ERGs were also reduced. The dark-adapted oscillatory potentials were reduced. The amplitudes of the mfERGs were severely depressed except at the fovea in both eyes.


These findings indicate that the RPE atrophy was wider and the rod dysfunction was more severe affected than that of previously reported MELAS cases with the m.3243A > G mutation.


Mitochondrial DNA 3271 MELAS M.3271delT Retinopathy 



We thank Professor Emeritus Duco Hamasaki of the Bascom Palmer Eye Institute of the University of Miami, FL, for discussions and editing the manuscript. This study was supported partly by Intramural Research Grant (29-4) for Neurological and Psychiatric Disorders of NCNP.

Compliance with ethical standards

Conflict of Interest

All authors declare that he/she has no conflict of interest.

Ethical approval

All procedures performed in these studies involving human participants were in accordance with the ethical standards of the Institutional and/or National Research Committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

10633_2019_9673_MOESM1_ESM.pptx (109 kb)
Supplementary material 1 (PPTX 109 kb)


  1. 1.
    Holt IJ, Harding AE, Morgan-Hughes JA (1988) Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies. Nature 331(6158):717–719CrossRefGoogle Scholar
  2. 2.
    Wallace DC, Singh G, Lott MT, Hodge JA, Schurr TG, Lezza AM, Elsas LJ II, Nikoskelainen EK (1988) Mitochondrial DNA mutation associated with Leber’s hereditary optic neuropathy. Science 242(4884):1427–1430CrossRefGoogle Scholar
  3. 3.
    Goto Y, Nonaka I, Horai S (1990) A mutation in the tRNA(Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature 348(6302):651–653CrossRefGoogle Scholar
  4. 4.
    Nesbitt V, Pitceathly RD, Turnbull DM, Taylor RW, Sweeney MG, Mudanohwo EE, Rahman S, Hanna MG, McFarland R (2013) The UK MRC mitochondrial disease patient cohort study: clinical phenotypes associated with the m.3243A > G mutation–implications for diagnosis and management. J Neurol Neurosurg Psychiatry 84(8):936–938. CrossRefGoogle Scholar
  5. 5.
    Goto Y, Nonaka I, Horai S (1991) A new mtDNA mutation associated with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Biochim Biophys Acta 1097(3):238–240CrossRefGoogle Scholar
  6. 6.
    Sakuta R, Goto Y, Horai S, Nonaka I (1993) Mitochondrial DNA mutations at nucleotide positions 3243 and 3271 in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes: a comparative study. J Neurol Sci 115(2):158–160CrossRefGoogle Scholar
  7. 7.
    Shinmei Y, Kase M, Suzuki Y, Nitta T, Chin S, Yoshida K, Goto Y, Nagashima T, Ohno S (2007) Ocular motor disorders in mitochondrial encephalopathy with lactic acid and stroke-like episodes with the 3271 (T-C) point mutation in mitochondrial DNA. J Neuroophthalmol 27(1):22–28CrossRefGoogle Scholar
  8. 8.
    Shoffner JM, Bialer MG, Pavlakis SG, Lott M, Kaufman A, Dixon J, Teichberg S, Wallace DC (1995) Mitochondrial encephalomyopathy associated with a single nucleotide pair deletion in the mitochondrial tRNALeu(UUR) gene. Neurology 45(2):286–292CrossRefGoogle Scholar
  9. 9.
    Akanuma J, Muraki K, Komaki H, Nonaka I, Goto Y (2000) Two pathogenic point mutations exist in the authentic mitochondrial genome, not in the nuclear pseudogene. J Hum Genet 45:337–341CrossRefGoogle Scholar
  10. 10.
    McCulloch DL, Marmor MF, Brigell MG, Hamilton R, Holder GE, Tzekov R, Bach M (2015) ISCEV Standard for full-field clinical electroretinography (2015 update). Doc Ophthalmol 130(1):1–12CrossRefGoogle Scholar
  11. 11.
    Hori N, Komori S, Yamada H, Sawada A, Nomura Y, Mochizuki K, Yamamoto T (2012) Assessment of macular function of glaucomatous eyes by multifocal electroretinograms. Doc Ophthalmol 125:235–247CrossRefGoogle Scholar
  12. 12.
    Hood DC, Bach M, Brigell M, Keating D, Kondo M, Lyons JS, Marmor MF, McCulloch DL, Palmowski-Wolfe AM (2012) International society for clinical electrophysiology of vision ISCEV standard for clinical multifocal electroretinography (mfERG) (2011 edition). Doc Ophthalmol 124:1–13CrossRefGoogle Scholar
  13. 13.
    Smith PR, Bain SC, Good PA, Hattersley AT, Barnett AH, Gibson JM, Dodson PM (1999) Pigmentary retinal dystrophy and the syndrome of maternally inherited diabetes and deafness caused by the mitochondrial DNA 3243 tRNA(Leu) A to G mutation. Ophthalmology 106(6):1101–1108CrossRefGoogle Scholar
  14. 14.
    Massin P, Virally-Monod M, Vialettes B, Paques M, Gin H, Porokhov B, Caillat-Zucman S, Froguel P, Paquis-Fluckinger V, Gaudric A, Guillausseau PJ (1999) Prevalence of macular pattern dystrophy in maternally inherited diabetes and deafness GEDIAM Group. Ophthalmology 106(9):1821–1827CrossRefGoogle Scholar
  15. 15.
    de Laat P, Smeitink JA, Janssen MC, Keunen JE, Boon CJ (2013) Mitochondrial retinal dystrophy associated with the m,3243A > G mutation. Ophthalmology 120(12):2684–2696CrossRefGoogle Scholar
  16. 16.
    Bellmann C, Neveu MM, Scholl HP, Hogg CR, Rath PP, Jenkins S, Bird AC, Holder GE (2004) Localized retinal electrophysiological and fundus autofluorescence imaging abnormalities in maternal inherited diabetes and deafness. Invest Ophthalmol Vis Sci 45(7):2355–2360CrossRefGoogle Scholar
  17. 17.
    Latvala T, Mustonen E, Uusitalo R, Majamaa K (2002) Pigmentary retinopathy in patients with the MELAS mutation 3243A > G in mitochondrial DNA. Graefes Arch Clin Exp Ophthalmol 240(10):795–801CrossRefGoogle Scholar
  18. 18.
    Yonemura D, Aoki T, Tsuzuki K (1962) Electroretinogram in diabetic retinopathy. Arch Ophthalmol 68:19–24CrossRefGoogle Scholar
  19. 19.
    Bresnick GH, Korth K, Groo A, Palta M (1984) Electroretinographic oscillatory potentials predict progression of diabetic retinopathy: preliminary report. Arch Ophthalmol 102(9):1307–1311CrossRefGoogle Scholar
  20. 20.
    Bresnick GH, Palta M (1987) Oscillatory potential amplitudes: relation to severity of diabetic retinopathy. Arch Ophthalmol 105(7):929–933CrossRefGoogle Scholar
  21. 21.
    Sakuta R, Nonaka I (1989) Vascular involvement in mitochondrial myopathy. Ann Neurol 25(6):594–601CrossRefGoogle Scholar
  22. 22.
    Koga Y, Akita Y, Junko N, Yatsuga S, Povalko N, Fukiyama R, Ishii M, Matsuishi T (2006) Endothelial dysfunction in MELAS improved by l-arginine supplementation. Neurology 66(11):1766–1769CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of OphthalmologyGifu University Graduate School of MedicineGifuJapan
  2. 2.Department of Neurology and GeriatricsGifu University Graduate School of MedicineGifuJapan
  3. 3.Departments of Neuromuscular Research, National Institute of Neurology and PsychiatryNational Center of Neurology and PsychiatryTokyoJapan
  4. 4.Mental Retardation and Birth Defect Research, National Institute of Neurology and PsychiatryNational Center of Neurology and PsychiatryTokyoJapan
  5. 5.Medical Genome CenterNational Center of Neurology and PsychiatryTokyoJapan

Personalised recommendations