An 11p15 imprinting centre region 2 deletion in a family with Beckwith Wiedemann syndrome provides insights into imprinting control at CDKN1C

PLoS One. 2011;6(12):e29034. doi: 10.1371/journal.pone.0029034. Epub 2011 Dec 19.

Abstract

We report a three generation family with Beckwith Wiedemann syndrome (BWS) in whom we have identified a 330 kb deletion within the KCNQ1 locus, encompassing the 11p15.5 Imprinting Centre II (IC2). The deletion arose on the paternal chromosome in the first generation and was only associated with BWS when transmitted maternally to subsequent generations. The deletion on the maternal chromosome was associated with a lower median level of CDKN1C expression in the peripheral blood of affected individuals when compared to a cohort of unaffected controls (p<0.05), however was not significantly different to the expression levels in BWS cases with loss of methylation (LOM) within IC2 (p<0.78). Moreover the individual with a deletion on the paternal chromosome did not show evidence of elevated CDKN1C expression or features of Russell Silver syndrome. These observations support a model invoking the deletion of enhancer elements required for CDKN1C expression lying within or close to the imprinting centre and importantly extend and validate a single observation from an earlier study. Analysis of 94 cases with IC2 loss of methylation revealed that KCNQ1 deletion is a rare cause of loss of maternal methylation, occurring in only 3% of cases, or in 1.5% of BWS overall.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Beckwith-Wiedemann Syndrome / genetics*
  • Chromosomes, Human, Pair 11 / genetics*
  • Cyclin-Dependent Kinase Inhibitor p57 / genetics*
  • DNA Methylation / genetics
  • Female
  • Gene Expression Regulation / genetics
  • Genomic Imprinting / genetics*
  • Haplotypes / genetics
  • Humans
  • KCNQ1 Potassium Channel / deficiency
  • KCNQ1 Potassium Channel / genetics
  • Male
  • Pedigree*
  • Sequence Deletion / genetics*

Substances

  • Cyclin-Dependent Kinase Inhibitor p57
  • KCNQ1 Potassium Channel