Bliek Jet, Gicquel Christine, Maas Saskia, Gaston Véronique, Le Bouc Yves, Mannens Marcel
Departments of Clinical Genetics and Anatomy & Embryology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
J Pediatr. 2004 Dec;145(6):796-9. doi: 10.1016/j.jpeds.2004.08.007.
Patients with Beckwith-Wiedemann syndrome (BWS) have a risk of 7.5% to 10% of developing childhood tumors, 60% of which are Wilms' tumors. Aberrant methylation of two distinct clusters of imprinted genes on chromosome 11p15 is detected in approximately 70% of BWS cases. Our aim was to determine associations between the imprinting status of both imprinting clusters (BWSIC1/2) and the tumor incidence and type.
Methylation patterns of H19 and KCNQ1OT1 were collected in 114 patients with BWS with a clinical diagnosis. The patients were followed until 5 years of age, and tumor incidence and type were registered.
A lower risk of developing childhood tumors was found among patients with a methylation defect limited to BWSIC2 compared with other patients with BWS. No Wilms' tumors were found in this group, whereas in patients with a methylation defect limited to BWSIC1 Wilms' tumor was the most common tumor.
In addition to clinical factors indicative for a high tumor risk (hemihypertrophy, nephromegaly), methylation patterns discriminate between patients with BWS with a high and low tumor risk. It also is possible to predict whether they are at risk of developing a Wilms' tumor. Epigenotyping of patients is important to select the type of screening protocol to be proposed to these patients.
贝克威思-维德曼综合征（BWS）患者患儿童肿瘤的风险为7.5%至10%，其中60%为肾母细胞瘤。在约70%的BWS病例中检测到11号染色体p15上两个不同的印记基因簇的异常甲基化。我们的目的是确定两个印记簇（BWSIC1/2）的印记状态与肿瘤发生率及类型之间的关联。
收集114例临床诊断为BWS患者的H19和KCNQ1OT1甲基化模式。对患者进行随访至5岁，并记录肿瘤发生率及类型。
与其他BWS患者相比，甲基化缺陷仅限于BWSIC2的患者患儿童肿瘤的风险较低。该组未发现肾母细胞瘤，而甲基化缺陷仅限于BWSIC1的患者中，肾母细胞瘤是最常见的肿瘤。
除了提示高肿瘤风险的临床因素（半身肥大、肾肿大）外，甲基化模式可区分高肿瘤风险和低肿瘤风险的BWS患者。还可以预测他们是否有患肾母细胞瘤的风险。对患者进行表观基因分型对于选择向这些患者推荐的筛查方案类型很重要。
