Lessons from BWS twins: complex maternal and paternal hypomethylation and a common source of haematopoietic stem cells
Lessons from BWS twins: complex maternal and paternal hypomethylation and a common source of haematopoietic stem cells
复制标题
DOI：
10.1038/ejhg.2009.77
复制
发表时间：
2009-12-01
影响因子：
5.2
通讯作者：
Mannens, Marcel M. A. M.
中科院分区：
文献类型：
--
作者：
Bliek, Jet;Alders, Marielle;Mannens, Marcel M. A. M.
Beckwith-Wiedemann 综合征 (BWS) 是一种生长障碍，据报道单卵双胞胎 (MZ) 的频率增加。除了少数例外，这些双胞胎的 BWS 和女性的表现不一致。在这里，我们描述了 12 个 BWS 双胞胎和一个三胞胎的分子和表型分析；七对双胞胎是同卵双胞胎，单绒毛膜和双羊膜，三对双胞胎是同卵双胞胎，双绒毛膜和双羊膜，三对双胞胎是双卵双胞胎。十二对双胞胎都是女性。在大多数双胞胎中（13 对中的 11 对），染色体 11p15 上的缺陷是 DMR2 父系等位基因的低甲基化。 10 名双胞胎中有 5 名的印记位点存在额外的低甲基化；在大多数情况下，受影响的位点是母源甲基化的，但在两种情况下，检测到父源甲基化 DLK1 和 H19 DMR 的低甲基化，这是 BWS 中的一个新发现。在共享胎盘的同卵双胞胎的口腔拭子中，缺陷仅存在于受影响的双胞胎中；在双胞胎中均检测到类似的淋巴细胞低甲基化。低甲基化水平达到25%以下。通过血管连接进行的血细胞交换不能完全解释未受影响双胞胎的血细胞中发现的低甲基化程度。我们提出了一种额外的机制，通过这种机制，不一致的双胞胎中可能会发生仅限于血细胞的异常甲基化模式的共享。在 BWS 不一致的 MZ 三联体中，在未受影响的同胞之一中发现了中等水平的去甲基化；这个孩子表现出轻微的 BWS 症状。这一发现支持了甲基化错误继续发生并可能触发孪生过程的理论。欧洲人类遗传学杂志 (2009) 17, 1625-1634; doi：10.1038/ejhg.2009.77； 2009 年 6 月 10 日在线发布
The Beckwith-Wiedemann syndrome (BWS) is a growth disorder for which an increased frequency of monozygotic (MZ) twinning has been reported. With few exceptions, these twins are discordant for BWS and for females. Here, we describe the molecular and phenotypic analysis of 12 BWS twins and a triplet; seven twins are MZ, monochorionic and diamniotic, three twins are MZ, dichorionic and diamniotic and three twins are dizygotic. Twelve twins are female. In the majority of the twin pairs ( 11 of 13), the defect on chromosome 11p15 was hypomethylation of the paternal allele of DMR2. In 5 of 10 twins, there was additional hypomethylation of imprinted loci; in most cases, the loci affected were maternally methylated, but in two cases, hypomethylation of the paternally methylated DLK1 and H19 DMRs was detected, a novel finding in BWS. In buccal swabs of the MZ twins who share a placenta, the defect was present only in the affected twin; comparable hypomethylation in lymphocytes was detected in both the twins. The level of hypomethylation reached levels below 25%. The exchange of blood cells through vascular connections cannot fully explain the degree of hypomethylation found in the blood cell of the non-affected twin. We propose an additional mechanism through which sharing of aberrant methylation patterns in discordant twins, limited to blood cells, might occur. In a BWS-discordant MZ triplet, an intermediate level of demethylation was found in one of the non-affected sibs; this child showed mild signs of BWS. This finding supports the theory that a methylation error proceeds and possibly triggers the twinning process. European Journal of Human Genetics (2009) 17, 1625-1634; doi:10.1038/ejhg.2009.77; published online 10 June 2009