title: A novel microdeletion in the IGF2/H19 imprinting centre region defines a recurrent mutation mechanism in familial Beckwith-Wiedemann syndrome.
abstract: 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.
authors.affiliation: Department of Environmental Science, University of Naples 2, Caserta, Italy.
authors.forename: Agostina
authors.initials: A
authors.lastname: De Crescenzo
authors.forename: Filomena
authors.initials: F
authors.lastname: Coppola
authors.forename: Pietro
authors.initials: P
authors.lastname: Falco
authors.forename: Italo
authors.initials: I
authors.lastname: Bernardo
authors.forename: Gaetano
authors.initials: G
authors.lastname: Ausanio
authors.forename: Flavia
authors.initials: F
authors.lastname: Cerrato
authors.forename: Luigi
authors.initials: L
authors.lastname: Falco
authors.forename: Andrea
authors.initials: A
authors.lastname: Riccio
mesh_terms: D000328:Adult; D001506:Beckwith-Wiedemann Syndrome / Q000235:genetics*; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D023061:Gene Order; D018392:Genomic Imprinting / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics*; D024182:Uniparental Disomy / Q000235:genetics
chemical_list: C094335:H19 long non-coding RNA; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D007335:Insulin-Like Growth Factor II