title: A novel de novo point mutation of the OCT-binding site in the IGF2/H19-imprinting control region in a Beckwith-Wiedemann syndrome patient.
abstract: 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.
authors.affiliation: Division of Molecular Genetics & Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Higashimoto
authors.forename: K
authors.initials: K
authors.lastname: Jozaki
authors.forename: T
authors.initials: T
authors.lastname: Kosho
authors.forename: K
authors.initials: K
authors.lastname: Matsubara
authors.forename: T
authors.initials: T
authors.lastname: Fuke
authors.forename: D
authors.initials: D
authors.lastname: Yamada
authors.forename: H
authors.initials: H
authors.lastname: Yatsuki
authors.forename: T
authors.initials: T
authors.lastname: Maeda
authors.forename: Y
authors.initials: Y
authors.lastname: Ohtsuka
authors.forename: K
authors.initials: K
authors.lastname: Nishioka
authors.forename: K
authors.initials: K
authors.lastname: Joh
authors.forename: H
authors.initials: H
authors.lastname: Koseki
authors.forename: T
authors.initials: T
authors.lastname: Ogata
authors.forename: H
authors.initials: H
authors.lastname: Soejima
mesh_terms: D001506:Beckwith-Wiedemann Syndrome / Q000235:genetics*; D001665:Binding Sites / Q000235:genetics; D000076246:CCCTC-Binding Factor; D002880:Chromosomes, Human, Pair 11; D019175:DNA Methylation; D018392:Genomic Imprinting; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000378:metabolism; D018895:Microsatellite Repeats; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D017354:Point Mutation; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D056730:Silver-Russell Syndrome / Q000235:genetics
chemical_list: D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; C094335:H19 long non-coding RNA; C035170:IGF2 protein, human; D050814:Octamer Transcription Factor-3; D062085:RNA, Long Noncoding; D012097:Repressor Proteins; D007335:Insulin-Like Growth Factor II
keywords: Beckwith-Wiedemann syndrome; ICR1 methylation defect; IGF2/H19; OCT-binding site; Silver-Russell syndrome