Journal of the Neurological Sciences
Volume 205, Issue 1 , Pages 41-45 , 15 December 2002

Segregation of the ND4/11778 and the ND1/3460 mutations in four heteroplasmic LHON families

  • Anu Puomila

      Affiliations

    • Corresponding Author InformationCorresponding author. Department of Medical Genetics, University of Turku, Kiinamyllynkatu 10, FIN-20520 Turku, Finland. Tel.: +358-2-333-7456; fax: +358-2-333-7300.
    • Department of Medical Genetics, University of Turku, Turku, Finland
    • Laboratory of Genetics, Department of Biology, University of Turku, Turku, Finland
  • ,
  • Tommi Viitanen

      Affiliations

    • Department of Statistics, University of Turku, Turku, Finland
  • ,
  • Marja-Liisa Savontaus

      Affiliations

    • Department of Medical Genetics, University of Turku, Turku, Finland
    • Laboratory of Genetics, Department of Biology, University of Turku, Turku, Finland
  • ,
  • Eeva Nikoskelainen

      Affiliations

    • Department of Ophthalmology, Turku University Central Hospital, Turku, Finland
  • ,
  • Kirsi Huoponen

      Affiliations

    • Department of Medical Genetics, University of Turku, Turku, Finland
    • Laboratory of Genetics, Department of Biology, University of Turku, Turku, Finland

Received 28 May 2002 ,Revised 24 July 2002 ,Accepted 25 July 2002.

References 

  1. Wallace DC, Singh G, Lott MT, Hodge JA, Schurr TG, Lezza AMS, et al.  Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy. Science. 1988;242:1427–1430
  2. Howell N, Bindoff LA, McCullough DA, Brierley E, Johnson MA, Turnbull DM, et al.  Leber hereditary optic neuropathy: identification of the same mitochondrial ND1 mutation in six pedigrees. Am. J. Hum. Genet. 1991;49:939–950
  3. 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;48:1147–1153
  4. Johns DR, Neufeld MJ, Park RD. An ND-6 mitochondrial DNA mutation associated with Leber hereditary optic neuropathy. Biochem. Biophys. Res. Commun. 1992;187:1551–1557
  5. Newman NJ, Lott MT, Wallace DC. The clinical characteristics of pedigrees of Leber's hereditary optic neuropathy with the 11778 mutation. Am. J. Ophthalmol. 1991;111:750–762
  6. Smith KH, Johns DR, Heher KL, Miller NR. Heteroplasmy in Leber's hereditary optic neuropathy. Arch. Ophthalmol. 1993;111:1486–1490
  7. Nikoskelainen EK, Huoponen K, Juvonen V, Lamminen T, Nummelin K, Savontaus M-L. Ophthalmologic findings in Leber hereditary optic neuropathy, with special reference to mtDNA mutations. Ophthalmology. 1995;103:504–514
  8. Ciafaloni E, Ricci E, Shanske S, Moraes CT, Silvestri G, Hirano M, et al.  MELAS: clinical features, biochemistry, and molecular genetics. Ann. Neurol. 1992;31:391–398
  9. Larsson N-G, Andersen O, Holme E, Oldfors A, Wahlström J. Leber's hereditary optic neuropathy and complex I deficiency in muscle. Ann. Neurol. 1991;30:701–708
  10. Majander A, Huoponen K, Savontaus M-L, Nikoskelainen E, Wikström M. Electron transfer properties of NADH: ubiquinone reductase in the ND1/3460 and the ND4/11778 mutations of the Leber hereditary optic neuroretinopathy (LHON). FEBS Lett. 1991;292:289–292
  11. Degli Esposti M, Carelli V, Ghelli A, Ratta M, Crimi M, Sangiorgi S, et al.  Functional alterations of the mitochondrially encoded ND4 subunit associated with the Leber's hereditary optic neuropathy. FEBS Lett. 1994;352:375–379
  12. Cock HR, Cooper JM, Schapira AHV. The 14484 ND6 mtDNA mutation in Leber hereditary optic neuropathy does not affect fibroblast complex I activity. Am. J. Hum. Genet. 1995;57:1501–1502
  13. Oostra R-J, Van Galen MJM, Bolhuis PA, Bleeker-Wagemakers EM, Van den Bogert C. The mitochondrial DNA mutation ND6*14,484C associated with Leber hereditary optic neuropathy, leads to deficiency of complex I of the respiratory chain. Biochem. Biophys. Res. Commun. 1995;215:1001–1005
  14. Carelli V, Ghelli A, Ratta M, Bacchilega E, Sangiorgi S, Mancini R, et al.  Leber's hereditary optic neuropathy: biochemical effect of 11778/ND4 and 3460/ND1 mutations and correlation with the mitochondrial genotype. Neurology. 1997;48:1623–1632
  15. Brown MD, Trounce IA, Jun AS, Allen JC, Wallace DC. Functional analysis of lymphoblast and cybrid mitochondria containing the 3460, 11778, or 14484 Leber's hereditary optic neuropathy mitochondrial DNA mutation. J. Biol. Chem. 2000;275:39831–39836
  16. Olsson C, Johnsen E, Nilsson M, Wilander E, Syvänen A-C, Lagerström-Fermer M. The level of the mitochondrial mutation A3243G decreases upon ageing in epithelial cells from individuals with diabetes and deafness. Eur. J. Hum. Genet. 2001;9:917–921
  17. Rahman S, Poulton J, Marchington D, Suomalainen A. Decrease of 3243 A→G mtDNA mutation from blood in MELAS syndrome: a longitudinal study. Am. J. Hum. Genet. 2001;68:238–240
  18. Kobayashi Y, Sharpe H, Brown N. Single-cell analysis of intercellular heteroplasmy of mtDNA in Leber hereditary optic neuropathy. Am. J. Hum. Genet. 1994;55:206–209
  19. Ghosh SS, Fahy E, Bodis-Wollner I, Sherman J, Howell N. Longitudinal study of a heteroplasmic 3460 Leber hereditary optic neuropathy family by multiplexed primer-extension analysis and nucleotide sequencing. Am. J. Hum. Genet. 1996;58:325–334
  20. Howell N, Ghosh SS, Fahy E, Bindoff LA. Longitudinal analysis of the segregation of mtDNA mutations in heteroplasmic individuals. J. Neurol. Sci. 2000;172:1–6
  21. Jacobi FK, Leo-Kottler B, Mittelviefhaus K, Zrenner E, Meyer J, Pusch CM, et al.  Segregation patterns and heteroplasmy prevalence in Leber's hereditary optic neuropathy. Invest. Ophthalmol. Visual Sci. 2001;42:1208–1214
  22. Huoponen K, Puomila A, Savontaus M-L, Mustonen E, Kronqvist E, Nikoskelainen E. Genetic counselling in Leber hereditary optic neuropathy (LHON). Acta Ophthalmol. Scand. 2002;80:38–43
  23. Juvonen V, Huoponen K, Syvänen A-C, Nikoskelainen E, Savontaus M-L. Quantification of point mutations associated with Leber hereditary optic neuroretinopathy by solid-phase minisequencing. Hum. Genet. 1994;93:16–20
  24. Vilkki J, Savontaus M-L, Nikoskelainen EK. Genetic heterogeneity in Leber hereditary optic neuroretinopathy revealed by mitochondrial DNA polymorphism. Am. J. Hum. Genet. 1989;45:206–211
  25. Juvonen V, Nikoskelainen E, Lamminen T, Penttinen M, Aula P, Savontaus M-L. Tissue distribution of the ND4/11778 mutation in heteroplasmic lineages with Leber hereditary optic neuropathy. Hum. Mutat. 1997;9:412–417
  26. Lott MT, Voljavec AS, Wallace DC. Variable genotype of Leber's hereditary optic neuropathy patients. Am. J. Ophthalmol. 1990;109:625–631
  27. Howell N, Xu M, Halvorson S, Bodis-Wollner I, Sherman J. A heteroplasmic LHON family: tissue distribution and transmission of the 11778 mutation. Am. J. Hum. Genet. 1994;55:203–206
  28. Bendall KE, Macaulay VA, Sykes BC. Variable levels of a heteroplasmic point mutation in individual hair roots. Am. J. Hum. Genet. 1997;61:1303–1308
  29. Lagerström-Fermer M, Olsson C, Forsgren L, Syvänen A-C. Heteroplasmy of the human mtDNA control region remains constant during life. Am. J. Hum. Genet. 2001;68:1299–1301

PII: S0022-510X(02)00276-9

Journal of the Neurological Sciences
Volume 205, Issue 1 , Pages 41-45 , 15 December 2002