A novel de novo point mutation of the OCT-binding site in the IGF2/H19-imprinting control region in a Beckwith-Wiedemann syndrome patient

Clin Genet. 2014 Dec;86(6):539-44. doi: 10.1111/cge.12318. Epub 2013 Dec 4.


The IGF2/H19-imprinting control region (ICR1) functions as an insulator to methylation-sensitive binding of CTCF protein, and regulates imprinted expression of IGF2 and H19 in a parental origin-specific manner. ICR1 methylation defects cause abnormal expression of imprinted genes, leading to Beckwith-Wiedemann syndrome (BWS) or Silver-Russell syndrome (SRS). Not only ICR1 microdeletions involving the CTCF-binding site, but also point mutations and a small deletion of the OCT-binding site have been shown to trigger methylation defects in BWS. Here, mutational analysis of ICR1 in 11 BWS and 12 SRS patients with ICR1 methylation defects revealed a novel de novo point mutation of the OCT-binding site on the maternal allele in one BWS patient. In BWS, all reported mutations and the small deletion of the OCT-binding site, including our case, have occurred within repeat A2. These findings indicate that the OCT-binding site is important for maintaining an unmethylated status of maternal ICR1 in early embryogenesis.

Keywords: Beckwith-Wiedemann syndrome; ICR1 methylation defect; IGF2/H19; OCT-binding site; Silver-Russell syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Beckwith-Wiedemann Syndrome / genetics*
  • Binding Sites / genetics
  • CCCTC-Binding Factor
  • Chromosomes, Human, Pair 11
  • DNA Methylation
  • Genomic Imprinting
  • Humans
  • Insulin-Like Growth Factor II / genetics*
  • Insulin-Like Growth Factor II / metabolism
  • Microsatellite Repeats
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / metabolism
  • Point Mutation*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Silver-Russell Syndrome / genetics


  • CCCTC-Binding Factor
  • CTCF protein, human
  • H19 long non-coding RNA
  • IGF2 protein, human
  • Octamer Transcription Factor-3
  • RNA, Long Noncoding
  • Repressor Proteins
  • Insulin-Like Growth Factor II