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Nuzhnyi E.P.

Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia

Abramycheva N.Yu.

Research Center of Neurology, Russian Academy of Sciences, Moscow

Nikolaeva N.S.

Research Center of Neurology, Moscow, Russia

Ershova M.V.

Research Center of Neurology, Moscow, Russia

Klyushnikov S.A.

Research Center of Neurology, Moscow, Russia

Illarioshkin S.N.

Nauchnyĭ tsentr nevrologii RAMN

Fedotova E.Yu.

Research Center of Neurology, Moscow, Russia

Epigenetic regulation of clinical manifestations of Friedreich’s disease

Authors:

Nuzhnyi E.P., Abramycheva N.Yu., Nikolaeva N.S., Ershova M.V., Klyushnikov S.A., Illarioshkin S.N., Fedotova E.Yu.

More about the authors

Journal: S.S. Korsakov Journal of Neurology and Psychiatry. 2020;120(1): 20‑26

DOI: 10.17116/jnevro202012001120

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Table of contents

EPIGENETIC REGULATION OF CLINICAL MANIFESTATIONS OF FRIEDREICH’S DISEASE
EPIGENETIC REGULATION OF CLINICAL MANIFESTATIONS OF FRIEDREICH’S DISEASE

To cite this article:

Nuzhnyi EP, Abramycheva NYu, Nikolaeva NS, Ershova MV, Klyushnikov SA, Illarioshkin SN, Fedotova EYu. Epigenetic regulation of clinical manifestations of Friedreich’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2020;120(1):20‑26. (In Russ.)
https://doi.org/10.17116/jnevro202012001120

Подписка 2025-2 (S.S. Korsakov Journal of Neurology and Psychiatry)
 
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Objective. To study a methylation profile of FXN gene and its influence on the clinical phenotype of Friedreich’s desease (FD). Material and methods. The methylation pattern was analyzed in 17 patients with FD. Forty-five CpG-sites in the promoter region and the region of intron 1 of FXN: before the GAA-expansion (UP-GAA) and after the GAA-expansion (DOWN-GAA), were studied. Results. Correlations between the methylation level of CpG-sites in UP-GAA and DOWN-GAA and the number of GAA repeats in both expanded FXN alleles in patients with FD were found. An analysis revealed an earlier onset and a more severe course of FD in cases with hypermethylation of several CpG-sites in the UP-GAA region. The correlation between the methylation pattern and the presence of extraneural manifestations of FD was also revealed. In FD patients with cardiomyopathy, a hypomethylated CpG-site in the promoter region was found. In FD patients with carbohydrate metabolism disorders, two hypomethylated CpG-sites in the DOWN-GAA region were observed. Conclusion. The results indicate a significant contribution of epigenetic modifications of FXN to the clinical presentation of FA.

Keywords:

Friedreich’s disease
epigenetics
DNA methylation
trinucleotide repeat expansion
phenotype heterogeneity

Authors:

Nuzhnyi E.P.

Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia

Abramycheva N.Yu.

Research Center of Neurology, Russian Academy of Sciences, Moscow

Nikolaeva N.S.

Research Center of Neurology, Moscow, Russia

Ershova M.V.

Research Center of Neurology, Moscow, Russia

Klyushnikov S.A.

Research Center of Neurology, Moscow, Russia

Illarioshkin S.N.

Nauchnyĭ tsentr nevrologii RAMN

Fedotova E.Yu.

Research Center of Neurology, Moscow, Russia

List of references:

  1. Illarioshkin SN, Rudenskaya GE, Ivanova-Smolenskaya IA, Markova ED, Klyushnikov SA. Nasledstvennye ataksii i paraplegii. M.: MEDpress-inform, 2006. (In Russ.)
  2. Burk K. Friedreich Ataxia: current status and future prospects. Cerebellum & Ataxias. 2017;4:4. eCollection 2017. https://doi.org/10.1186/s40673-017-0062-x
  3. Ershova MV, Illarioshkin SN. Molekulyarnye osnovy bolezni Fridreikha. Zhurnal Nevrologii i Psikhiatrii im. S.S Korsakova. 2003;103(2):61-67. (In Russ.)
  4. Faraj SE, Roman EA, Aran M, Gallo M, Santos J. The alteration of the C-terminal region of human frataxin distorts its structural dynamics and function. FEBS J. 2014;281(15):3397-3419. https://doi.org/10.1111/febs.12869
  5. Heidari MM, Houshmand M, Hosseinkhani S, Nafissi S, Khatami M. Complex I and ATP content deficiency in lymphocytes from Friedreich’s ataxia. Can J Neurol Sci. 2009;36(1):26-31. https://doi.org/10.1017/s0317167100006260
  6. Parkinson MH, Boesch S, Nachbauer W, Mariotti C, Giunti P. Clinical features of Friedreich’s ataxia: classical and atypical phenotypes. J Neurochem. 2013;126(suppl 1):103-117. https://doi.org/10.1111/jnc.12317
  7. Weidemann F, Stork S, Liu D, Hu K, Herrmann S, Ertl G, Niemann M. Cardiomyopathy of Friedreich Ataxia. J Neurochem. 2013;126(suppl 1):88-93. https://doi.org/10.1111/jnc.12217
  8. Weidemann F, Rummey C, Bijnens B, Stork S, Jasaityte R, Dhooge J, Baltabaeva A, Sutherland G, Schulz JB, Meier T. The heart in Friedreich ataxia: definition of cardiomyopathy, disease severity, and correlation with neurological symptoms. Circulation. 2012;125:1626-1634. https://doi.org/10.1161/circulationaha.112.115287
  9. Fomicheva EI, Myasnikov RP, Selivyorstov YuA., Dadali EL, Kotalevskaya YuYu, Kharlap MS, Koretsky SN, Nuzhny EP, Mershina EA, Sinitsyn VE, Vernokhaeva AN, Bazaeva EV, Drapkina OM, Boytsov SA. Cardiomyopathy in the Friedreich ataxia: clinical presentation and diagnosis of complications. Rossiiskii Kardiologicheskii Zhurnal. 2017;10(150):100-106. (In Russ.) https://doi.org/10.15829/1560-4071-2017-10-100-106
  10. McCormick A, Farmer J, Perlman S, Delatycki M, Wilmot G, Matthews K, Yoon G, Hoyle C, Subramony SH, Zesiewicz T, Lynch DR, McCormack SE. Impact of diabetes in the Friedreich ataxia clinical outcome measures study. Annals of Clinical and Translational Neurology. 2017; 4(9): 622—631. https://doi.org/10.1002/acn3.439
  11. Dürr A, Cossee M, Agid Y, Campuzano V, Mignard C, Penet C, Mandel JL, Brice A, Koenig M. Clinical and Genetic Abnormalities in Patients with Friedreich’s Ataxia. N Engl J Med. 1996;335:1169-1175. https://doi.org/10.1056/NEJM199610173351601
  12. Pappa A, Hausler MG, Veigel A, Tzamouranis K, Pfeifer MW, Schmidt A, Bokamp M, Haberland H, Wagner S, Bruckel J, de Sousa G, Hackl L, Bollow E, Holl RW. Diabetes mellitus in Friedreich Ataxia: A case series of 19 patients from the German-Austrian diabetes mellitus registry. Diabetes Res Clin Pract. 2018;141:229-236. https://doi.org/10.1016/j.diabres.2018.05.008
  13. Isaacs CJ, Brigatti KW, Kucheruk O, Ratcliffe S, Sciascia T, McCormack SE, Willi SM, Lynch DR. Effects of genetic severity on glucose homeostasis in Friedreich ataxia. Muscle Nerve. 2016;54:887-894. https://doi.org/10.1002/mus.25136
  14. Filla A, De Michele G, Cavalcanti F, Pianese L, Monticelli A, Campanella G, Cocozza S. The relationship between trinucleotide (GAA) repeat length and clinical features in Friedreich ataxia. Am J Hum Genet. 1996;59(3):554-560. https://doi.org/10.1016/s0013-4694(97)88573-6
  15. Deutsch EC, Santani AB, Perlman SL, Farmer JM, Stolle CA, Marusich MF, Lynch DR. A rapid, noninvasive immunoassay for frataxin: utility in assessment of Friedreich ataxia. Mol Genet Metab. 2010;101:238-245. https://doi.org/10.1016/j.ymgme.2010.07.001
  16. Illarioshkin SN, Ershova MV, Bagyeva GKh, Markova ED, Klyushnikov SA, Ivanova-Smolenskaya IA. Atipichnye fenotipy bolezni Fridreykha: DNK-analiz i kliniko-geneticheskie sopostavleniya. Meditsinskaya Genetika. 2004;3(1):36-42. (In Russ.)
  17. Abrahao A, Pedroso JL, de Carvalho Aguiar PM, Barsottini OG. Gene Expression Profile in Peripheral Blood Cells of Friedreich Ataxia Patients. Cerebellum. 2016;15(3):306-313. https://doi.org/10.1007/s12311-015-0700-x
  18. Christopher MA, Kyle SM, Katz DJ. Neuroepigenetic mechanisms in disease. Epigenetics & Chromatin. 2017;10:47. https://doi.org/10.1186/s13072-017-0150-4
  19. Castaldo I, Pinelli M, Monticelli A, Acquaviva F, Giacchetti M, Filla A, Sacchetti S, Keller S, Avvedimento VE, Chiariotti L, Cocozza S. DNA methylation in intron 1 of the frataxin gene is related to GAA repeat length and age of onset in Friedreich ataxia patients. J Med Genet. 2008;45(12):808-812. https://doi.org/10.1136/jmg.2008.058594
  20. Evans-Galea MV, Carrodus N, Rowley SM, Corben LA, Tai G, Saffery R, Galati JC, Wong NC, Craig JM, Lynch DR, Regner SR, Brocht AF, Perlman SL, Bushara KO, Gomez CM, Wilmot GR, Li L, Varley E, Delatycki MB, Sarsero JP. FXN methylation predicts expression and clinical outcome in Friedreich ataxia. Ann Neurol. 2012;71(4):487-497. https://doi.org/10.1002/ana.22671
  21. Al-Mahdawi S, Pinto RM, Ismail O, Varshney D, Lymperi S, Sandi C, Trabzuni D, Pook M. The Friedreich ataxia GAA repeat expansion mutation induces comparable epigenetic changes in human and transgenic mouse brain and heart tissues. Human Molecular Genetics. 2008;17(5):735-746. https://doi.org/10.1093/hmg/ddm346
  22. Quesada MP, Jones J, Rodríguez-Lozano FJ, Moraleda JM, Martinez S. Novel aberrant genetic and epigenetic events in Friedreich´s ataxia. Experimental Cell Research. 2015;1:335(1):51-61. https://doi.org/10.1016/j.yexcr.2015.04.013
  23. Ucar A, Gupta SK, Fiedler J, Erikci E, Kardasinski M, Batkai S, Dangwal S, Kumarswamy R, Bang C, Holzmann A, Remke J, Caprio M, Jentzsch C, Engelhardt S, Geisendorf S, Glas C, Hofmann TG, Nessling M, Richter K, Schiffer M, Carrier L, Napp LC, Bauersachs J, Chowdhury K, Thum T. The miRNA-212/132 family regulates both cardiac hypertrophy and cardiomyocyte autophagy. Nature Communication. 2012;3:1078. https://doi.org/10.1038/ncomms2090

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