Aberrant methylation of H19-DMR acquired after implantation was dissimilar in soma versus placenta of patients with Beckwith-Wiedemann syndrome

American Journal of Medical Genetics. Part a
Ken HigashimotoHidenobu Soejima

Abstract

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.

References

Dec 13, 2006·Human Molecular Genetics·Angela SparagoAndrea Riccio
Jan 17, 2008·Nature Reviews. Genetics·Hiroyuki Sasaki, Yasuhisa Matsui
Jun 25, 2009·European Journal of Human Genetics : EJHG·Rosanna WeksbergJ Bruce Beckwith
Aug 31, 2010·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Bernhard Horsthemke
Aug 31, 2010·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Sanaa ChoufaniRosanna Weksberg
Oct 1, 2011·The Journal of Obstetrics and Gynaecology Research·Aiko AokiShigeru Saito

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Citations

May 31, 2013·Journal of Human Genetics·Hidenobu Soejima, Ken Higashimoto

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Beckwith-Wiedemann syndrome is an imprinting disorder characterized by overgrowth, congenital malformations and predisposition to tumors. Discover the latest research on Beckwith-Wiedemann Syndrome here.