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

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.

• Publication year

  2011

• Venue

  European Journal of Medical Genetics

• Publication date

  2011-07-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.ejmg.2011.04.009PMID 21571108PMCID 3133689
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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