Methylation analysis in tongue tissue of BWS patients identifies the (EPI)genetic cause in 3 patients with normal methylation levels in blood
Methylation analysis in tongue tissue of BWS patients identifies the (EPI)genetic cause in 3 patients with normal methylation levels in blood
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DOI：
10.1016/j.ejmg.2014.03.011
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发表时间：
2014-05-01
影响因子：
1.9
通讯作者：
Mannens, Marcel M. A. M.
中科院分区：
文献类型：
--
作者：
Alders, Marielle;Maas, Saskia M.;Mannens, Marcel M. A. M.
Beckwith-Wiedemann综合征是由11p15.5的基因印迹干扰引起的。Beckwith-Wiedemann综合征（BWS）的常规诊断测试包括从淋巴细胞提取的DNA中印迹中心ICR 1和ICR 2的甲基化分析。在大约15%的BWS患者中，诊断无法在分子水平上得到证实。在这项研究中，我们确定了11例BWS患者切除的舌组织中的甲基化状态，并将其与血液淋巴细胞常规诊断筛查发现的遗传缺陷进行了比较。在所有三名血液甲基化水平正常的患者中，舌组织中发现了异常甲基化模式。在两名患者中检测到UPD，第三例患者存在ICR 1高甲基化。这一结果表明，组织特异性镶嵌（epi）遗传变化，不存在于血液中，是至少一个子集的BWS患者的潜在缺陷，在标准基因检测后没有分子诊断。(C)2014年Elsevier Masson SAS。All rights reserved.
The Beckwith-Wiedemann syndrome is caused by disturbed imprinting of genes at 11p15.5. Routine diagnostic testing for Beckwith-Wiedemann syndrome (BWS) includes methylation analysis of the imprinting centers ICR1 and ICR2 in DNA extracted from lymphocytes. In approximately 15% of BWS patients the diagnosis cannot be molecularly confirmed. In this study we determined the methylation status in resected tongue tissue of 11 BWS patients and compared this to the genetic defects found by routine diagnostic screening of blood lymphocytes. In all three patients with normal methylation levels in blood, aberrant methylation patterns were found in tongue tissue. In two patients a UPD was detected and the third case had hypermethylation of ICR1. This result shows that tissue specific mosaic (epi) genetic changes, not present in blood, is the underlying defect in at least a subset of BWS patients without a molecular diagnosis after standard genetic testing. (C) 2014 Elsevier Masson SAS. All rights reserved.