ORIGINAL RESEARCH

Friedreich ataxia: FXN gene expression and its relationship with DNA methylation pattern

Fedotova EYu, Abramycheva NYu, Nuzhny EP, Ershova MV, Klyushnikov SA, Illarioshkin SN
About authors

Research Center of Neurology, Moscow, Russia

Correspondence should be addressed: Ekaterina Yu. Fedotova
Volokolamskoe shosse, 80, Moscow, 125367; moc.liamg@avotodefke

About paper

Funding: the study is supported by grant of the Russian Science Foundation (project № 17-75-20211).

Author contribution: all authors contributed to the study and preparation of the article equally, read and approved the final version before publishing.

Received: 2019-08-22 Accepted: 2019-09-13 Published online: 2019-09-26
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Friedreich ataxia (FRDA) is the most common autosomal recessive ataxia associated with the non-coding GAA tandem repeats expansion in the FXN gene. Transcription impairment and frataxin protein deficiency are the key features of the disease pathogenesis. Our research was aimed to study the FXN gene mRNA expression as well as to carry out the clinical, genetic and epigenetic correlation analysis in a group of patients with homozygous expansion, in a group of their relatives with heterozygous expansion and in a control group. The FXN mRNA level was determined using the real-time polymerase chain reaction. Methylation pattern of CpG sites was evaluated by direct bisulfite sequencing. As a result of the study, the threshold values were obtained between the FRDA patients group, the group of heterozygous carriers and the control group (15 and 79%, respectively). The clinical and genetic features comparison with the FXN expression level revealed no significant correlation. When comparing gene expression with an epigenetic profile, it was found that hypermethylation of a number of CpG sites upstream of the trinucleotide repeats and some non-CpG sites downstream of the region of repeats inhibited expression. Thus, the identified methylated sites may be considered as a target for epigenome editing to increase the FXN transcription and, consequently, for target therapy of the disease.

Keywords: gene expression, Friedreich ataxia, epigenetics, DNA methylation, non-CpG methylation, DNA diagnostics, target therapy

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