Acta Biologica Hungarica

, Volume 54, Issue 3–4, pp 253–262 | Cite as

Mitochondrial DNA4977 Deletion in Brain of Newborns Died After Intensive Care

  • Edit A. Nádasi
  • B. Melegh
  • L. Seress
  • G. KosztolányiEmail author


Mitochondrial DNA (mtDNA) deletion affecting 4977 base pairs (mtDNA4977), the most common mtDNA mutation in humans, was analysed in brain specimens (frontal, temporal, and cerebellar cortices, caudate nucleus, thalamus, and hippocampus) and in other tissues (blood clot, liver, kidney, heart, and muscle) taken at autopsy of deceased neonates. mtDNA4977 deletion determined by polymerase chain reaction (PCR) could be demonstrated in each neonatal sample, however, quantity of mtDNA4977 deletion was less in the newborn samples than in those of the elderlies. Results obtained suggest that contrary to certain data mtDNA4977 deletion can be present in neonates. The mtDNA4977 deletion could be generated by perinatal hypoxia or temporary oxygen oversaturations during the intensive care of the neonates, as the mtDNA is sensitive to oxidative damage. In combination with other factors an additional causative role of mtDNA4977 deletion reported here cannot be ruled out in development of cerebral palsy or mental retardation of unknown origin often seen in neonates underwent neonatal intensive care procedures.


Mitochondrial DNA deletion ageing brain damage perinatal hypoxia intensive care 


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The work was supported by OTKA grant No. 32556.


  1. 1.
    Ames, B. N., Shigenaga, M. K., Hagen, T. M. (1995) Mitochondrial decay in aging. Biochim. Biophys. Acta 1271, 165–170.CrossRefGoogle Scholar
  2. 2.
    Calloway, C. D., Reynolds, R. L., Herrin, G. L., Abderson, W. W. (2000) The frequency of hetero-plasmy in the HVII region of mtDNA differs across tissue types and increases with age. Am. J. Hum. Genet. 66, 1384–1397.CrossRefGoogle Scholar
  3. 3.
    Chinnery, P. F., Zwijnenburg, P. J. G., Walker, M., Howell, N., Taylor, R. W., Lightowlers, R. N., Bindoff L., Turnbull, D. M. (1999) Nonrandom tissue distribution of mutant mtDNA. Am. J. Med Genet. 85, 498–501.CrossRefGoogle Scholar
  4. 4.
    Corral-Debrinski, M., Horton, T., Lott, M. T., Shoffner, J. M., Beal, M. E., Wallace, D. C. (1992) Mitochondrial DNA deletions in human brain: regional variability and increase with advanced age. Nat. Genet. 2, 324–329.CrossRefGoogle Scholar
  5. 5.
    Cortopassi, G., Shibata, D., Soong, N. W., Arnheim, N. (1992) A. pattern of accumulation of a. somat-ic deletion of mitochondrial DNA in aging human tissues. Proc. Natl. Acad. Sci. USA 89, 7370–7374.CrossRefGoogle Scholar
  6. 6.
    Erikkson, R. S., Perilieva, E., Björk-Erikkson, T., Alborn, A.-M., Nordborg, C., Peterson, D. A., Gage, F. H. (1998) Neurogenesis in the adult human hippocampus. Nat. Med 4, 1313–1317.CrossRefGoogle Scholar
  7. 7.
    Lightowlers, R. N., Jacobs, H. T., Kajander, O. A. (1999) Mitochondrial DNA - all things bad? Trends Genet. 15, 91–93.CrossRefGoogle Scholar
  8. 8.
    MacLennan, A. for the International Cerebral Palsy Task Force (1999) A. template for defming a. casual relation between acute intrapartum events and cerebral palsy: international consensus statement. BMJ 319, 1054–1059.CrossRefGoogle Scholar
  9. 9.
    McKee, A. C., Beal, M. F., Graham, B. H., Wallace, D. C. (1994) Marked changes in mitochondrial DNA deletion levels in Alzheimer brains. Genomics 23, 471–476.CrossRefGoogle Scholar
  10. 10.
    Méhes, K., Bajnóczky, K., Adamovich, K., Khezri, S., Kosztolanyi, G. (1999) No latent chromosome damage in oxygen-exposed premature neonates. J. Hum. Genet. 44, 40–12.CrossRefGoogle Scholar
  11. 11.
    Meisser, C., von Wurmb, N. (1998) Sensitive Detection of the 4977-bp Deletion in human mito-chondrial DNA of young individuals. Bio Techniques 25, 652–654.Google Scholar
  12. 12.
    Nagley, R., Wei, Y. H. (1998) Ageing and mitochondrial genetics. Trends Genet. 14, 1–5.CrossRefGoogle Scholar
  13. 13.
    Seress, L. (2001) Morphological changes in the human hippocampal formation from midgestation to early childhood. In: Nelson, C. A. and Luciana, M. (eds) Handbook of Developmental Cognitive Neuroscience. MIT Press, Cambridge-London, pp. 45–58.Google Scholar
  14. 14.
    Shenkar, R., Navidi, W., Tavaré, S., Dang, M. H., Chomyn, A., Attarfï, G., Cortopassi, G., Arnheim, N. (1996) The mutation rate of the human mtDNA deletion mtDNA4977. Am. J. Hum. Gene. 59, 772–780.Google Scholar
  15. 15.
    Simonetti, S., Chen, X., DiMauro, S., Schon, E. A. (1992) Accumulation of deletions in human mitochondrial DNA during normal aging: analysis by quantitative PCR. Biochim. Biophys. Acta 1180, 113–122.CrossRefGoogle Scholar
  16. 16.
    Soong, N. W., Arnheim, N. (1995) Quantitative PCR: analysis of rare mitochondrial DNA mutations in central nervous system tissues. Methods in Neurosciences 26, 105–127.CrossRefGoogle Scholar
  17. 17.
    Soong, N. W., Hinton, D. R., Cortopassi, G., Arnheim, N. (1992) Mosaicism for a. specific somatic mitochondrial DNA mutation in adult human brain. Nat. Genet. 2, 318–323.CrossRefGoogle Scholar
  18. 18.
    Stepien, G., Shoffner, J. M., Lott, M. T., Kanter, K., Wallace, D. C. (1991) Hypoxaemia is associat-ed with mitochondrial DNA damage and gene induction. JAMA 266, 1812–1816.CrossRefGoogle Scholar
  19. 19.
    Stromme, P., Hagberg, G. (2000) Aetiology in severe and mild mental retardation: a. population-based study of Norwegian children. Dev. Med. ChildNeurol. 42, 76–86.CrossRefGoogle Scholar
  20. 20.
    Takeda, N., Tanamura, A., Iwai, T., Nakamura, I., Kato, M., Ohkubo, T., Noma, K. (1993) Mitochondrial DNA deletion in human myocardium. Mol. Cell. 119, 105–108.Google Scholar
  21. 21.
    Veelken, B. N., Schopf M., Dammann, O., Schulte, F. J. (1993) Etiological classification of cerebral palsy in very low birthweight infants. Neuropediatrics 24, 74–76.CrossRefGoogle Scholar
  22. 22.
    Wallace, D. C., Shoffner, J. M., Trounce, I., Brown, M. D., Ballinger, S. W., Corral-Debrinski, M., Horton, T., Jun, A. S., Lott, M. T. (1995) Mitochondrial DNA mutations in human degenerative dis-eases and aging. Biochim. Biophys. Acta 1271, 141–151.CrossRefGoogle Scholar
  23. 23.
    Yang, J. H., Lee, H. C., Lin, K. J., Wei, Y. H. (1994) A. specific 4977-bp deletion of mitochondrial DNA in human aging skin. Arch. Dermatol. Res. 286, 386–390.CrossRefGoogle Scholar

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© Akadémiai Kiadó, Budapest 2003

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Authors and Affiliations

  • Edit A. Nádasi
    • 1
  • B. Melegh
    • 1
  • L. Seress
    • 2
  • G. Kosztolányi
    • 1
    • 3
    Email author
  1. 1.Department of Medical Genetics and Child DevelopmentMedical CenterPécsHungary
  2. 2.Central Electronmicroscopic Laboratory, Faculty of MedicineUniversity of PécsPécsHungary
  3. 3.MTA-PTE Clinical Genetics Research GroupPécsHungary

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