Screening of DNA Methylation at the H19 Promoter or the Distal Region of its ICR1 Ensures Efficient Detection of Chromosome 11p15 Epimutations in Russell-Silver Syndrome
Screening of DNA Methylation at the H19 Promoter or the Distal Region of its ICR1 Ensures Efficient Detection of Chromosome 11p15 Epimutations in Russell-Silver Syndrome
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DOI：
10.1002/ajmg.a.33065
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发表时间：
2009-11-01
影响因子：
2
通讯作者：
Weksberg, Rosanna
中科院分区：
文献类型：
--
作者：
Horike, Shin-Ichi;Ferreira, Jose Carlos P.;Weksberg, Rosanna
在10年的时间里，从57名患有生长受限和RSS样特征的人身上采集了血液样本。我们的目标是识别这个队列中的表观遗传学异常，包括7号染色体的单亲二体(UPD7)，染色体1p15的甲基化变化，以及新的表观基因组变化。我们评估了7号、11号、14号和15号染色体上7个印迹控制区的甲基化状态。UPD7和7号染色体结构异常已在5名患者中被发现。在I-I患者中发现了染色体11p15上的表观遗传学改变。有趣的是，在这些I-I患者中，3名患者的表观遗传学改变仅限于H19启动子及其相关印记中心ICR1的远端区域。此外，在一名患者中，我们在所有测试的印迹区域检测到与母体UPD一致的甲基化变化。这一病例系列表明，通过筛查H19启动子或ICR远端区域的DNA甲基化缺陷，可以最有效地检测RSS患者染色体11p15上的表观突变。(C)2009年Wiley-Liss，Inc.
Over a 10-year period blood samples were collected from 57 individuals with growth restriction and RSS-like features. Our goal was to identify epigenetic abnormalities in this cohort, including uniparental disomy of chromosome 7 (UPD7), methylation changes at chromosomel 1p15, as well as new epigenomic alterations. We evaluated the methylation status of 7 imprinting control regions on chromosomes 7, 11, 14, and 15. UPD7 and chromosome 7 structural abnormalities had been previously identified in five patients. Epigenetic alterations on chromosome 11p15 were identified in I I patients. Of interest, in 3 of these I I patients, the epigenetic alterations were limited to the H19 promoter and the distal region of its associated imprinting center, ICR1. In addition, in one patient, we detected methylation changes consistent with maternal UPD at all tested imprinted regions. This patient series suggests that epimutations on chromosome 11p15 can be most efficiently detected in RSS patients by screening for DNA methylation defects at the H19 promoter or the distal region of ICR. (C) 2009 Wiley-Liss, Inc.