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Aberrant methylation of H19‐DMR acquired after implantation was dissimilar in soma versus placenta of patients with Beckwith–Wiedemann syndrome
Author(s) -
Higashimoto Ken,
Nakabayashi Kazuhiko,
Yatsuki Hitomi,
Yoshinaga Hokuto,
Jozaki Kosuke,
Okada Junichiro,
Watanabe Yoriko,
Aoki Aiko,
Shiozaki Arihiro,
Saito Shigeru,
Koide Kayoko,
Mukai Tsunehiro,
Hata Kenichiro,
Soejima Hidenobu
Publication year - 2012
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.35335
Subject(s) - methylation , genomic imprinting , epigenetics , dna methylation , beckwith–wiedemann syndrome , imprinting (psychology) , placenta , differentially methylated regions , biology , cancer research , genetics , fetus , pregnancy , gene , gene expression
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.