期刊
CLINICAL GENETICS
卷 86, 期 6, 页码 539-544出版社
WILEY-BLACKWELL
DOI: 10.1111/cge.12318
关键词
Beckwith-Wiedemann syndrome; ICR1 methylation defect; IGF2; H19; OCT-binding site; Silver-Russell syndrome
资金
- Ministry of Health, Labor, and Welfare
- National Center for Child Health and Development
- Japan Society for the Promotion of Science
- Grants-in-Aid for Scientific Research [22132004, 23249015, 26670169, 23659181, 22227002] Funding Source: KAKEN
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.
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