title: Aberrant methylation of H19-DMR acquired after implantation was dissimilar in soma versus placenta of patients with Beckwith-Wiedemann syndrome.
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.
authors.affiliation: Division of Molecular Genetics & Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Higashimoto
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakabayashi
authors.forename: Hitomi
authors.initials: H
authors.lastname: Yatsuki
authors.forename: Hokuto
authors.initials: H
authors.lastname: Yoshinaga
authors.forename: Kosuke
authors.initials: K
authors.lastname: Jozaki
authors.forename: Junichiro
authors.initials: J
authors.lastname: Okada
authors.forename: Yoriko
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Aiko
authors.initials: A
authors.lastname: Aoki
authors.forename: Arihiro
authors.initials: A
authors.lastname: Shiozaki
authors.forename: Shigeru
authors.initials: S
authors.lastname: Saito
authors.forename: Kayoko
authors.initials: K
authors.lastname: Koide
authors.forename: Tsunehiro
authors.initials: T
authors.lastname: Mukai
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Hata
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Soejima
mesh_terms: D000483:Alleles; D001506:Beckwith-Wiedemann Syndrome / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D018392:Genomic Imprinting; D005838:Genotype; D006801:Humans; D010920:Placenta / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics*
chemical_list: C094335:H19 long non-coding RNA; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated