Bliek J, Maas S M, Ruijter J M, Hennekam R C, Alders M, Westerveld A, Mannens M M
Department of Clinical Genetics, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands.
Hum Mol Genet. 2001 Mar 1;10(5):467-76. doi: 10.1093/hmg/10.5.467.
Beckwith-Wiedemann syndrome (BWS) is an overgrowth malformation syndrome that maps to human chromosome 11p15.5, a region that harbours a number of imprinted genes. We studied the methylation status of H19 and KCNQ1OT1 (LIT1/KvDMR1) in a large series of BWS patients. Different patient groups were identified: group I patients (20%) with uniparental disomy and hence aberrant methylation of H19 and KCNQ1OT1; group II patients (7%) with a BWS imprinting centre 1 (BWSIC1) defect causing aberrant methylation of H19 only; group III patients (55%) with a BWS imprinting centre 2 (BWSIC2) defect causing aberrant methylation of KCNQ1OT1 only; and group IV patients (18%) with normal methylation patterns for both H19 and KCNQ1OT1. BWS patients have an increased risk of developing childhood tumours. In our patient group, out of 31 patients (group III) with KCNQ1OT1 demethylation only, none developed a tumour. However, tumours were found in 33% of patients with H19 hypermethylation (group I and II) and in 20% of patients with no detectable genetic defect (group IV). All four familial cases of BWS showed reduced methylation of KCNQ1OT1, suggesting that in these cases the imprinting switch mechanism is disturbed.
贝克威思-维德曼综合征（BWS）是一种过度生长畸形综合征，定位于人类11号染色体短臂15.5区，该区域包含多个印记基因。我们研究了一大组BWS患者中H19和KCNQ1OT1（LIT1/KvDMR1）的甲基化状态。确定了不同的患者组：I组患者（20%）存在单亲二体，因此H19和KCNQ1OT1甲基化异常；II组患者（7%）存在BWS印记中心1（BWSIC1）缺陷，仅导致H19甲基化异常；III组患者（55%）存在BWS印记中心2（BWSIC2）缺陷，仅导致KCNQ1OT1甲基化异常；IV组患者（18%）H19和KCNQ1OT1甲基化模式正常。BWS患者患儿童肿瘤的风险增加。在我们的患者组中，31例仅KCNQ1OT1去甲基化的患者（III组）均未发生肿瘤。然而，H19高甲基化患者（I组和II组）中有33%发生了肿瘤，无可检测基因缺陷的患者（IV组）中有20%发生了肿瘤。所有4例BWS家族病例均显示KCNQ1OT1甲基化降低，提示在这些病例中印记开关机制受到干扰。
