Expanded [CCTG]n repetitions are not associated with abnormal methylation at the CNBP locus in myotonic dystrophy type 2 (DM2) patients

Massimo Santoro, Luana Fontana, Francesca Maiorca, Federica Centofanti, Roberto Massa, Gabriella Silvestri, Giuseppe Novelli, Annalisa Botta

Research output: Contribution to journalArticlepeer-review


Myotonic Dystrophy type 2 (DM2) is a multisystemic disorder associated with an expanded [CCTG]n repeat in intron 1 of the CNBP gene. Epigenetic modifications have been reported in many repeat expansion disorders, including myotonic dystrophy type 1 (DM1), either as a mechanism to explain somatic repeat instability or transcriptional alterations in disease genes. The purpose of our work was to determine the effect of DM2 mutation on the methylation status of CpG islands localized in the 5' promoter region and in the 3' end of the [CCTG]n expansion of the CNBP gene. By bisulfite pyrosequencing, we characterized the methylation profile of two different CpG islands within these regions, either in whole blood and skeletal muscle tissues of DM2 patients (n=72 and n=7, respectively) and controls (n=50 and n=7, respectively). Moreover, we compared the relative mRNA transcript levels of CNBP gene in leukocytes and in skeletal muscle tissues from controls and DM2 patients. We found that CpG sites located in the promoter region showed hypomethylation, whereas CpG sites at 3' end of the CCTG array are hypermethylated. Statistical analyses did not demonstrate any significant differences in the methylation profile between DM2 patients and controls in both tissues analyzed. According to the methylation analysis, CNBP gene expression levels are not significantly altered in DM2 patients. These results show that [CCTG]n repeat expansion, differently from the DM1 mutation, does not influence the methylation status of the CNBP gene and suggest that other molecular mechanisms are involved in the pathogenesis of DM2.

Original languageEnglish
Pages (from-to)917-924
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Issue number3
Publication statusPublished - Mar 2018


  • Case-Control Studies
  • CpG Islands
  • DNA Methylation/genetics
  • DNA Repeat Expansion/genetics
  • Female
  • Genetic Association Studies
  • Genetic Loci
  • Humans
  • Male
  • Middle Aged
  • Myotonic Dystrophy/genetics
  • RNA-Binding Proteins/genetics
  • Sequence Analysis, DNA


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