Zheleznyakova GY, Nilsson EK, Kiselev AV, Maretina MA, Tishchenko LI, Fredriksson R, Baranov VS, Schiöth HB
PLoS ONE 10 (3) e0121964 [2015-03-30; online 2015-03-30]
Spinal muscular atrophy (SMA) is a monogenic neurodegenerative disorder subdivided into four different types. Whole genome methylation analysis revealed 40 CpG sites associated with genes that are significantly differentially methylated between SMA patients and healthy individuals of the same age. To investigate the contribution of methylation changes to SMA severity, we compared the methylation level of found CpG sites, designed as "targets", as well as the nearest CpG sites in regulatory regions of ARHGAP22, CDK2AP1, CHML, NCOR2, SLC23A2 and RPL9 in three groups of SMA patients. Of notable interest, compared to type I SMA male patients, the methylation level of a target CpG site and one nearby CpG site belonging to the 5'UTR of SLC23A2 were significantly hypomethylated 19-22% in type III-IV patients. In contrast to type I SMA male patients, type III-IV patients demonstrated a 16% decrease in the methylation levels of a target CpG site, belonging to the 5'UTR of NCOR2. To conclude, this study validates the data of our previous study and confirms significant methylation changes in the SLC23A2 and NCOR2 regulatory regions correlates with SMA severity.