Increased Prevalence 12308 A > G mutation in Mitochondrial tRNALeu (CUN) Gene Associated with earlier Age of Onset in Friedreich Ataxia

Mohammad Medhi HEIDARI, Mehri KHATAMI, Massoud HOUSHMAND, Eisa MAHMOUDI, Shahriar NAFISSI

Abstract


375

How to Cite this Article: Heidari MM, Khatami M, Houshmand M, Mahmoudi E, Nafissi Sh .Increased Prevalence 12308 A > G mutation in MitochondrialtRNALeu (CUN) Gene Associated with earlier Age of Onset in Friedreich Ataxia. Iranian Journal of Child Neurology 2011;5(4):25-31.Objective Friedreich ataxia (FRDA) is an inherited recessive disorder. Mitochondrial DNA is a candidate modifying factor for FRDA.The purpose of this study was to investigate the relationship between the tRNALeu (CUN) 12308 A> G mutation and age of onset in Friedreich ataxia.Materials & Methods The 12308 A> G substitution in mitochondrial tRNALeu (CUN) was examined in DNA samples from 30 Friedreich ataxia patients and 48 control subjects by temporal temperature gradient gel electrophoresis (TTGE) and sequencing. Logistic regression was used to determine of cutoff age of onset.ResultsTwenty-two patients had the 12308 A> G mutation, and we found that its overall prevalence was significantly higher in 20 patients aged 17 years or younger than in 2 patients aged over 17 years (90% versus 10%). The 12308 A> G mutation lies in a region that has been highly conserved between species.Conclusion Our results show that the 12308 A > G mutation is associated with earlier age of onset in Friedreich ataxia. Thus, this mutation might cause the younger age of onset in FRDA.

References

  1. Grabczyk E, Usdin K. The GAA*TTC triplet repeat expanded in Friedreich ataxia impedes transcription elongation by T7 RNA polymerase in a length and supercoil dependent manner. Nucleic Acids Res 2000;28(14):2815-22.
  2. Sakamoto N, Chastain PD, Parniewski P, Ohshima K, Pandolfo M, Griffith JD, et al. Sticky DNA: self association properties of long GAA.TTC repeats in R.R.Y triplex structures from Friedreich ataxia. Mol Cell1999;3(4):465-75.
  3. Lodi R, Cooper JM, Bradley JL, Manners D, Styles P, Taylor DJ, et al. Deficit of in vivo mitochondrial ATP production in patients with Friedreich ataxia. Proc Natl Acad Sci U S A 1999;96(20):11492-5.
  4. Babcock M, de Silva D, Oaks R, Davis-Kaplan S, Jiralerspong S, Montermini L, et al. Regulation of mitochondrial iron accumulation by Yfh1p, a putative homolog of frataxin. Science 1997;276(5319):1709-12.
  5. Wilson RB, Roof DM. Respiratory deficiency due to loss of mitochondrial DNA in yeast lacking the frataxin homologue. Nat Genet 1997;16(4):352-7.
  6. Ramazzotti A, Vanmansart V, Foury F. Mitochondrial functional interactions between frataxin and Isu1p, the iron-sulfur cluster scaffold protein, in Saccharomycescerevisiae. FEBS Lett 2004;557(1-3):215-20.
  7. Foury F, Cazzalini O. Deletion of the yeast homologue of the human gene associated with Friedreich ataxiaelicits iron accumulation in mitochondria. FEBS Lett1997;411(2-3):373-7.
  8. Foury F, Talibi D. Mitochondrial control of iron homeostasis. A genome wide analysis of gene expression in a yeast frataxin-deficient strain. J Biol Chem 2001;276(11):7762-8.
  9. Koeppen AH. Friedreich ataxia: pathology, pathogenesis, and molecular genetics. J Neurol Sci 2011;303(1-2):1-12.
  10. Kish SJ, Bergeron C, Rajput A, Dozic S, Mastrogiacomo F, Chang LJ, et al. Brain cytochrome oxidase in Alzheimer’s disease. J Neurochem 1992;59(2):776-9.
  11. Schapira AH. Mitochondrial complex I deficiency in Parkinson’s disease. Adv Neurol 1993;60(1):288-91.
  12. Lu F, Selak M, O’Connor J, Croul S, Lorenzana C, Butunoi C, et al. Oxidative damage to mitochondrial DNA and activity of mitochondrial enzymes in chronicactive lesions of multiple sclerosis. J Neurol Sci2000;177(2):95-103.
  13. Bradley JL, Blake JC, Chamberlain S, Thomas PK, Cooper JM, Schapira AH. Clinical, biochemical and molecular genetic correlations in Friedreich ataxia. Hum Mol Genet 2000;9(2):275-82.
  14. Rotig A, de Lonlay P, Chretien D, Foury F, Koenig M, Sidi D, et al. Aconitase and mitochondrial iron-sulphur protein deficiency in Friedreich ataxia. Nat Genet1997;17(2):215-7.
  15. van den Ouweland JM, Bruining GJ, Lindhout D, Wit JM, Veldhuyzen BF, Maassen JA. Mutations in mitochondrial tRNA genes: non-link age with syndromes of Wolfram and chronic progressive external ophthalmoplegia. Nucleic Acids Res 1992;20(4):679-82.
  16. Harding AE. Friedreich ataxia: a clinical and genetic study of 90 families with an analysis of early diagnostic criteria and intrafamilial clustering of clinical features. Brain 1981;104(3):589-620.
  17. Geoffroy G, Barbeau A, Breton G, Lemieux B, Aube M, Leger C, et al. Clinical description and roentgenologic evaluation of patients with Friedreich ataxia. Can J Neurol Sci 1976;3(4):279-86.
  18. Campuzano V, Monter mini L, Molto MD, Pianese L, Cossee M, Cavalcanti F, et al. Friedreich ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science 1996;271(5254):1423-7.
  19. Tan DJ, Bai RK, Wong LJ. Comprehensive scanning of somatic mitochondrial DNA mutations in breast cancer. Cancer Res 2002;62(4):972-6.
  20. Sanchez M, Anitua E, Azofra J, Andia I, Padilla S, Mujika I. Comparison of surgically repaired Achilles tendon tearsusing platelet-rich fibrin matrices. Am J Sports Med2007;35(2):245-51.
  21. Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR, Drouin J, et al. Sequence and organization of the human mitochondrial genome. Nature1981;290(5806):457-65.22. Marmolino D. Friedreich ataxia: past, present and future.Brain Res Rev 2011;67(1-2):311-30.
  22. Houshmand M, Mahmoudi T, Panahi MS, Seyedena Y,Saber S, Ataei M. Identification of a new human mt DNA polymorphism (A14290G) in the NADH dehydrogenase subunit 6 gene. Braz J Med Biol Res 2006;39(6):725-30.
  23. Rona RJ, Reynolds A, Allsop M, Morris RW, Morgan M, Mandalia S. Audit from preschool developmental surveillance of vision, hearing, and language referrals. Arch Dis Child 1991;66(8):921-6.
  24. Heidari MM, Houshmand M, Hosseinkhani S, Nafissi S, Scheiber-Mojdehkar B, Khatami M. A novel mitochondrial heteroplasmic C13806A point mutation associated with Iranian Friedreich ataxia. Cell Mol Neurobiol 2009;29(2):225-33.
  25. Covarrubias D, Bai RK, Wong LJ, Leal SM. Mitochondrial DNA variant interactions modify breast cancer risk. J Hum Genet 2008;53(10):924-8.
  26. Pulkes T, Sweeney MG, Hanna MG. Increased risk of stroke in patients with the A12308G polymorphism in mitochondria. Lancet 2000;356(9247):2068-9.
  27. Wei YH. Oxidative stress and mitochondrial DNA mutations in human aging. Proc Soc Exp Biol Med1998;217(1):53-63.
  28. Hess JF, Parisi MA, Bennett JL, Clayton DA. Impairment of mitochondrial transcription termination by a point mutation associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature 1991;351(6323):236-9.

 


Keywords


Friedreich ataxia; tRNALeu (CUN) gene; mitochondrial DNA; Mutation; TTGE

Full Text:

PDF

219



DOI: https://doi.org/10.22037/ijcn.v5i4.2674

Refbacks

  • There are currently no refbacks.


Copyright (c)