The authors have no competing financial interests to declare.
A novel de novo point mutation of the OCT-binding site in the IGF2/H19-imprinting control region in a Beckwith–Wiedemann syndrome patient
Article first published online: 4 DEC 2013
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
How to Cite
A novel de novo point mutation of the OCT-binding site in the IGF2/H19-imprinting control region in a Beckwith–Wiedemann syndrome patient., , , , , , , , , , , , , .
- Article first published online: 4 DEC 2013
- Accepted manuscript online: 8 NOV 2013 08:55AM EST
- Manuscript Revised: 6 NOV 2013
- Manuscript Accepted: 6 NOV 2013
- Manuscript Received: 5 AUG 2013
- Ministry of Health, Labor, and Welfare
- National Center for Child Health and Development
- Japan Society for the Promotion of Science
- Beckwith–Wiedemann syndrome;
- ICR1 methylation defect;
- OCT-binding site;
- Silver–Russell syndrome
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.