title: Increased tumour risk for BWS patients correlates with aberrant H19 and not KCNQ1OT1 methylation: occurrence of KCNQ1OT1 hypomethylation in familial cases of BWS.
abstract: Beckwith-Wiedemann syndrome (BWS) is an overgrowth malformation syndrome that maps to human chromosome 11p15.5, a region that harbours a number of imprinted genes. We studied the methylation status of H19 and KCNQ1OT1 (LIT1/KvDMR1) in a large series of BWS patients. Different patient groups were identified: group I patients (20%) with uniparental disomy and hence aberrant methylation of H19 and KCNQ1OT1; group II patients (7%) with a BWS imprinting centre 1 (BWSIC1) defect causing aberrant methylation of H19 only; group III patients (55%) with a BWS imprinting centre 2 (BWSIC2) defect causing aberrant methylation of KCNQ1OT1 only; and group IV patients (18%) with normal methylation patterns for both H19 and KCNQ1OT1. BWS patients have an increased risk of developing childhood tumours. In our patient group, out of 31 patients (group III) with KCNQ1OT1 demethylation only, none developed a tumour. However, tumours were found in 33% of patients with H19 hypermethylation (group I and II) and in 20% of patients with no detectable genetic defect (group IV). All four familial cases of BWS showed reduced methylation of KCNQ1OT1, suggesting that in these cases the imprinting switch mechanism is disturbed.
authors.affiliation: Department of Clinical Genetics, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Bliek
authors.forename: S M
authors.initials: SM
authors.lastname: Maas
authors.forename: J M
authors.initials: JM
authors.lastname: Ruijter
authors.forename: R C
authors.initials: RC
authors.lastname: Hennekam
authors.forename: M
authors.initials: M
authors.lastname: Alders
authors.forename: A
authors.initials: A
authors.lastname: Westerveld
authors.forename: M M
authors.initials: MM
authors.lastname: Mannens
mesh_terms: D000483:Alleles; D001483:Base Sequence; D001506:Beckwith-Wiedemann Syndrome / Q000150:complications / Q000235:genetics*; D019175:DNA Methylation; D017931:DNA Primers; D005260:Female; D020022:Genetic Predisposition to Disease; D018392:Genomic Imprinting; D006801:Humans; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D008297:Male; D009369:Neoplasms / Q000150:complications / Q000235:genetics*; D010375:Pedigree; D015221:Potassium Channels / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics*
chemical_list: D017931:DNA Primers; C094335:H19 long non-coding RNA; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated