A novel de novo point mutation of the OCT-binding site in the IGF2/H19-imprinting control region in a Beckwith-Wiedemann syndrome patient

作者：Higashimoto K; Jozaki K; Kosho T; Matsubara K; Fuke T; Yamada D; Yatsuki H; Maeda T; Ohtsuka Y; Nishioka K; Joh K; Koseki H; Ogata T; Soejima H^*

来源：Clinical Genetics, 2014, 86(6): 539-544.

DOI：10.1111/cge.12318

• Beckwith-Wiedemann syndrome
• ICR1 methylation defect
• IGF2
• H19
• OCT-binding site
• Silver-Russell syndrome

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.

• 出版日期2014-12