Abstract
Purpose To define the prevalence of a panel of mitochondrial DNA (mtDNA) mutations associated with Leber's hereditary optic neuropathy (LHON) in the Turkish LHON population. LHON-associated mtDNA mutations have been found in LHON patients from around the world, but the Turkish LHON population has not been studied.
Methods Thirty-two Turkish patients were defined clinically as having LHON on the basis of painless, subacute, bilateral optic neuropathy and the exclusion of other causes of subacute optic neuropathy. mtDNA was extracted from blood of the 32 probands and assayed for a panel of primary and secondary LHON-associated mtDNA mutations by polymerase chain reaction (PCR)-based methods. We studied three well-known LHON-associated primary mutations (at nucleotide positions 11778, 3460 and 14484) and one common secondary mutation (at nucleotide 15257) in all 32 probands. In addition to these mutations, 18 of the 32 probands were tested for the Complex IV, COX III gene, LHON associated 9804 and 9438 mutations and secondary LHON mutations at nucleotide positions 3394, 4160, 4216, 4917, 5244, 7444, 7706, 13708, 13730 and 15812.
Results Among the 32 probands tested for four common LHON mutations, 3 carried the 14484 mutation, 1 carried the 11778 mutation, 1 carried the 3460 mutation and 1 carried the 15257 mutation. Among the 18 LHON patients who tested for additional mutations, 1 proband harboured the 9804 mutation and 4 carried the secondary mutations at nucleotide positions 4216, 4917 and 13708.
Conclusion The results of mtDNA analysis of the Turkish LHON patients appear to be different from those of previous reports.
Similar content being viewed by others
Article PDF
References
Wallace DC, Singh G, Lott MT, et al. Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy. Science 1988;242:1427–30.
Huoponen K, Vilkki J, Aula P, Nikoskelainen EK, Savontaus M-L . A new mtDNA mutation associated with Leber hereditary optic neuroretinopathy. Am J Hum Genet 1991;48:1147–53.
Howell N, Bindoff LA, McCullough DA, et al. Leber hereditary optic neuropathy: identification of the same mitochondrial ND1 mutation in six pedigrees. Am J Hum Genet 1991;49:939–50.
Vilkki J, Savontaus M-L, Nikoskelainen EK . Segregation of mitochondrial genomes in a heteroplasmic lineage with Leber hereditary optic neuroretinopathy. Am J Hum Genet 1990;47:95–100.
Mackey D, Howell N . A variant of Leber hereditary optic neuropathy characterised by recovery of vision and by an unusual mitochondrial genetic etiology. Am J Hum Genet 1992;51:1218–28.
Johns DR, Neufeld MJ . Cytochrome c oxidase mutations in Leber's hereditary optic neuropathy. Biochem Biophys Res Commun 1993;196:810–5.
Johns DR, Neufeld MJ . Cytochrome b mutations in Leber hereditary optic neuropathy. Biochem Biophys Res Commun 1991;181:1358–64.
Brown MD, Voljavec AS, Lott MT, Torroni A, Yang C-C, Wallace DC . Mitochondrial DNA complex I and III mutations associated with Leber's hereditary optic neuropathy. Genetics 1992;130:163–73.
Johns DR, Berman J . Alternative, simultaneous complex I mitochondrial DNA mutations in Leber's hereditary optic neuropathy. Biochem Biophys Res Commun 1991;174:1324–30.
Brown MD, Yang C-C, Trounce I, Torroni A, Lott MT, Wallace DC . A mitochondrial DNA variant, identified in Leber hereditary optic neuropathy patients, which extends the amino acid sequence of cytochrome c oxidase subunit I. Am J Hum Genet 1992;51:378–85.
Brown MD, Wallace DC . Spectrum of mitochondrial DNA mutations in Leber's hereditary optic neuropathy. Clin Neurosci 1994;2:138–45.
Johns DR, Smith KH, Savino PJ, Miller NR . Leber's hereditary optic neuropathy. Clinical manifestations of the 15257 mutation Ophthalmology 1993;100:981–6.
Brown MD, Voljavec AS, Lott MT, McDonald I, Wallace DC . Leber's hereditary optic neuropathy: a model for mitochondrial neurodegenerative diseases. FASEB J 1992;6:2791–8.
Oostra RJ, Bolhuis PA, Wijburg FA, Zorn-Ende G, Bleeker-Wagemakers EM . Leber's hereditary optic neuropathy: correlations between mitochondrial genotype and visual outcome. J Med Genet 1994;31:280–6.
Oostra RJ, Bolhuis PA, Zorn-Ende I, de Kok-Nazaruk MM, Bleeker-Wagemakers EM . Leber's hereditary optic neuropathy: no significant evidence for primary or secondary pathogenicity of the 15257 mutation. Hum Genet 1994;94:265–70.
Anderson S, Bankier AT, Barrell BG, et al. Sequence and organisation of the human mitochondrial genome. Nature 1981;290:457–65.
Harding AE, Sweeney MG, Govan GG, Riordan-Eva P . Pedigree analysis in Leber hereditary optic neuropathy with a pathogenic mtDNA mutation. Am J Hum Genet 1995;56:72–6.
Vilkki J, Savontaus M-L, Nikoskelainen EK . Genetic heterogeneity in Leber hereditary optic neuropathy revealed by a mitochondrial DNA polymorphism. Am J Hum Genet 1989;45:206–11.
Nakamura M, Ara F, Yamada M, et al. High frequency of mitochondrial ND4 mutation in Japanese pedigrees with Leber hereditary optic neuropathy. Jpn J Ophthalmol 1992;36:56–61.
Nikoskelainen EK, Marttila RJ, Huoponen K, et al. Leber's ‘plus’: neurological abnormalities in patients with Leber's hereditary optic neuropathy. J Neurol Neurosurg Psychiatry 1995;59:160–4
Macmillan C, Kirkham T, Fu K, et al. Pedigree analysis of French Canadian families with T14484C Leber's hereditary optic neuropathy. Neurology 1998;50:417–22.
Author information
Authors and Affiliations
Corresponding author
Additional information
A part of this work was presented at the 1997 AAN Meeting
Rights and permissions
About this article
Cite this article
Dogulu, C., Kansu, T., Seyrantepe, V. et al. Mitochondrial DNA analysis in the Turkish Leber's hereditary optic neuropathy population. Eye 15, 183–188 (2001). https://doi.org/10.1038/eye.2001.57
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/eye.2001.57
Keywords
This article is cited by
-
Leber hereditary optic neuropathy—new insights and old challenges
Graefe's Archive for Clinical and Experimental Ophthalmology (2021)
-
Fifteen novel mutations in the mitochondrial NADH dehydrogenase subunit 1, 2, 3, 4, 4L, 5 and 6 genes from Iranian patients with Leber’s hereditary optic neuropathy (LHON)
Molecular Biology Reports (2013)