A novel microdeletion in the IGF2/H19 imprinting centre region defines a recurrent mutation mechanism in familial Beckwith-Wiedemann syndrome.
A novel microdeletion in the IGF2/H19 imprinting centre region defines a recurrent mutation mechanism in familial Beckwith-Wiedemann syndrome.
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DOI：
10.1016/j.ejmg.2011.04.009
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发表时间：
2011-07
影响因子：
1.9
通讯作者：
Riccio A
中科院分区：
文献类型：
--
作者：
De Crescenzo A;Coppola F;Falco P;Bernardo I;Ausanio G;Cerrato F;Falco L;Riccio A
过度生长障碍的Beckwith-Wiedemann综合征(BWS)与染色体11p15.5上印记基因的失调有关。分子缺陷是异质性的，但大多数病例与两个印迹控制区(IC1和IC2)中的一个区域的DNA甲基化缺陷或11p15.5处的单亲父亲二体(UPD)有关。在极少数情况下，已发现BWS表型与IC1微缺失的母体传播有关。我们描述了一个新的1.8kb缺失的家庭，该缺失与IC1的高甲基化相关。该突变是由含有锌指蛋白CTCF(CTSS)靶点的高度同源序列之间的重组引起的。这一发现支持这样的假设，即IC1的功能和临床表型的外显性取决于突变等位基因重组产生的CTS的间距。
The overgrowth disorder Beckwith–Wiedemann syndrome (BWS) is associated with dysregulation of imprinted genes at chromosome 11p15.5. The molecular defects are heterogeneous but most of the cases are associated with defective DNA methylation at either one of two Imprinting Control Regions (IC1 and IC2) or Uniparental paternal Disomy (UPD) at 11p15.5. In rare cases, the BWS phenotype has been found associated with maternal transmission of IC1 microdeletions. We describe a family with a novel 1.8 kb deletion that is associated with hypermethylation at IC1. The mutation results from recombination between highly homologous sequences containing target sites for the zinc-finger protein CTCF (CTSs). This finding supports the hypothesis that the function of IC1 and the penetrance of the clinical phenotype depend on the spacing of the CTSs resulting from recombination in the mutant allele.