Objective: To compare methylation profiles in frataxin (FXN) and ataxin-2 (ATXN2) genes in patients with spinocerebellar ataxia type 2 (SCA2), Friedreich’s ataxia (FA) and a healthy control group.

Background: Pathogenic GAA expansion in the FXN gene and CAG expansion in the gene ATXN2 cause FA and SCA2 respectively. A wide range of clinical characteristics is only partially explained by the CAG and GAA expansion size alone. Methylation profile of ATXN2 and FXN may play a role in the pathogenesis and the clinical presentation of SCA2 and FA, but it has not been studied enough.

Methods: We analysed the DNA methylation status of the FA samples (n=10) by performing bisulfate sequence analysis of two regions of the FXN gene: a 808 bp sequence upstream of the microsatellite (GAA)n repeats containing 18 CpG sites and a 252 bp sequence downstream of the (GAA)n repeats containing 12 CpG sites. Also we investigated methylation of the promoter of ATXN2 expansions in SCA2 patients (n=13). The analysis of ATXN2 and FXN methylation was also performed in healthy age- and sex-matched control samples (n=10).

Results: In the upstream region of FXN, multiple CpG sites showed significantly higher methylation in FA compared to control samples (all CpG sites were methylated in FA and 4 of 18 sites were unmethylated in the control group). The downstream region showed significantly lower methylation in FA compared to control samples (3 of 12 CpG sites had no methylation in all FA cases). There were no cases of ATXN2 promoter methylation in the SCA2 and the control groups.

Conclusions: This is the first data on the methylation of ATXN2 and FXN expansions in Russian population. We suggest that FXN methylation may play a role in the FA pathogenesis.

References: The study was supported by RSF 17-75- 20211.

« Back to 2018 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/fxn-and-atxn2-methylation-profile-in-friedreichs-ataxia-and-spinocerebellar-ataxia-type-2/