How to Cite this Article: Higashimoto K, Nakabayashi K, Yatsuki H, Yoshinaga H, Jozaki K, Okada J, Watanabe Y, Aoki A, Shiozaki A, Saito S, Koide K, Mukai T, Hata K, Soejima H. 2012. Aberrant methylation of H19-DMR acquired after implantation was dissimilar in soma versus placenta of patients with Beckwith–Wiedemann syndrome. Am J Med Genet Part A. 158A:1670–1675.
Aberrant methylation of H19-DMR acquired after implantation was dissimilar in soma versus placenta of patients with Beckwith–Wiedemann syndrome†
Article first published online: 10 MAY 2012
Copyright © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 158A, Issue 7, pages 1670–1675, July 2012
How to Cite
Higashimoto, K., Nakabayashi, K., Yatsuki, H., Yoshinaga, H., Jozaki, K., Okada, J., Watanabe, Y., Aoki, A., Shiozaki, A., Saito, S., Koide, K., Mukai, T., Hata, K. and Soejima, H. (2012), Aberrant methylation of H19-DMR acquired after implantation was dissimilar in soma versus placenta of patients with Beckwith–Wiedemann syndrome. Am. J. Med. Genet., 158A: 1670–1675. doi: 10.1002/ajmg.a.35335
- Issue published online: 18 JUN 2012
- Article first published online: 10 MAY 2012
- Manuscript Accepted: 19 JAN 2012
- Manuscript Received: 7 OCT 2011
- Japan Society for the Promotion of Science. Grant Number: 20590330
- Ministry of Health, Labor, and Welfare
- National Center for Child Health and Development
- Beckwith–Wiedemann syndrome;
- aberrant DNA methylation;
- after implantation
Gain of methylation (GOM) at the H19-differentially methylated region (H19-DMR) is one of several causative alterations in Beckwith–Wiedemann syndrome (BWS), an imprinting-related disorder. In most patients with epigenetic changes at H19-DMR, the timing of and mechanism mediating GOM is unknown. To clarify this, we analyzed methylation at the imprinting control regions of somatic tissues and the placenta from two unrelated, naturally conceived patients with sporadic BWS. Maternal H19-DMR was abnormally and variably hypermethylated in both patients, indicating epigenetic mosaicism. Aberrant methylation levels were consistently lower in placenta than in blood and skin. Mosaic and discordant methylation strongly suggested that aberrant hypermethylation occurred after implantation, when genome-wide de novo methylation normally occurs. We expect aberrant de novo hypermethylation of H19-DMR happens to a greater extent in embryos than in placentas, as this is normally the case for de novo methylation. In addition, of 16 primary imprinted DMRs analyzed, only H19-DMR was aberrantly methylated, except for NNAT DMR in the placental chorangioma of Patient 2. To our knowledge, these are the first data suggesting when GOM of H19-DMR occurs. © 2012 Wiley Periodicals, Inc.