A novel microdeletion in the IGF2/H19 imprinting centre region defines a recurrent mutation mechanism in familial Beckwith-Wiedemann syndrome

被引：31

作者：

De Crescenzo, Agostina ^{[1
]}

Coppola, Filomena ^{[2
]}

Falco, Pietro ^{[2
]}

Bernardo, Italo ^{[2
]}

Ausanio, Gaetano ^{[2
]}

Cerrato, Flavia ^{[1
]}

Falco, Luigi ^{[2
]}

Riccio, Andrea ^{[1
,3
]}

机构：

[1] Univ Naples 2, Dept Environm Sci, I-81100 Caserta, Italy

[2] Azienda Osped Caserta, UO Neonatol & Terapia Intens Neonatale, Caserta, Italy

[3] CNR, Inst Genet & Biophys, I-80125 Naples, Italy

来源：

EUROPEAN JOURNAL OF MEDICAL GENETICS | 2011年 / 54卷 / 04期

关键词：

Epigenetics; Genomic imprinting; Growth disorders; CHROMOSOME; 11P15;

D O I：

10.1016/j.ejmg.2011.04.009

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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. (C) 2011 Elsevier Masson SAS. All rights reserved.

引用

页码：E451 / E454

页数：4

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