Methylation of the CpG sites in the myotonic dystrophy locus does not correlate with CTG expansion size or with the congenital form of the disease

J Med Genet. 2010 Oct;47(10):700-3. doi: 10.1136/jmg.2009.074211. Epub 2010 Jul 19.

Abstract

We have studied the methylation status of the sequence 152 nucleotides upstream of the CTG repeat of the DM1 locus in patients' peripheral blood. We used the methylation-sensitive endonucleases SacII, HpaII and HhaI, followed by PCR. This allowed to correlate the methylation status of each CTG allele with its size. Contrary to previous findings, only the SacII site is often but not always differentially methylated among expanded CTG alleles. Importantly, this methylation was not restricted to congenital DM1, nor to large expansions, as it was also present in DM1 patients with a classical phenotype and various expansion sizes. On the other hand, we did not find any methylated alleles on the HhaI and HpaII sites, as was reported by Steinbach et al, which is in line with the results of Shaw and collaborators. The size range of the repeat expansions with methylation was from as small as 300 to as large as 2800 repeats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Dinucleoside Phosphates / genetics
  • Dinucleoside Phosphates / metabolism*
  • Endonucleases / metabolism
  • Humans
  • Methylation
  • Molecular Sequence Data
  • Myotonic Dystrophy / genetics*
  • Myotonic Dystrophy / pathology
  • Myotonin-Protein Kinase
  • Phenotype
  • Polymerase Chain Reaction
  • Protein Serine-Threonine Kinases / chemistry
  • Protein Serine-Threonine Kinases / genetics*
  • Trinucleotide Repeat Expansion / genetics*
  • Trinucleotide Repeats

Substances

  • DMPK protein, human
  • Dinucleoside Phosphates
  • cytidylyl-3'-5'-guanosine
  • Myotonin-Protein Kinase
  • Protein Serine-Threonine Kinases
  • Endonucleases