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Published on: April 21, 2016
[Epigenetic regulation of clinical manifestations of Friedreich's disease]
E P Nuzhny1, N Yu Abramycheva1, N S Nikolaeva1
1Research Center of Neurology, Moscow, Russia.
Aim:
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.
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