Positional cloning of genes involved in the Beckwith-Wiedemann syndrome, hemihypertrophy, and associated childhood tumors

Marcel Mannens, Marielle Alders, Bert Redeker, Jet Bliek, Marja Steenman, Carien Wiesmeyer, Maurice De Meulemeester, Andy Ryan, Linda Kalikin, Tom Voûte, Jan De Kraker, Jan Hoovers, Rosalyn Slater, Andy Feinberg, Peter Little, Andries Westerveld

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

The Beckwith-Wiedemann syndrome (BWS) is an overgrowth malformation syndrome that occurs with an incidence of 1:13,700 births. There is a striking incidence of childhood tumors found in BWS patients. Various lines of investigation have localized 'imprinted' genes involved in BWS and associated childhood tumors to 11p15. High resolution mapping of 8 rare balanced chromosomal BWS rearrangements enabled us to identify three distinct regions on chromosome 11p15 that might harbor genes involved in the above- mentioned disorders. These results suggest genetic heterogeneity that correlates with the clinical heterogeneity seen in the patients studied. Expressed candidate gene sequences from these regions have been cloned and partly sequenced. These transcripts are either disrupted by or are at least within a few kb of these BWS chromosome breakpoints. So far, zinc-finger sequences and one Kruppel-associated box (KRAB) domain were found in independent candidate genes which are compatible with a regulating function of growth promoting genes. The abundance of expression of these genes varies from low abundant in all adult and fetal tissues tested to detectable on Northern blots of adult tissues. In addition to our 11p15 studies we have analyzed additional chromosome regions, in particular 1p. Cytogenetic, loss of heterozygosity (LOH) and comparative genomic hybridization (CGH) studies have identified 1p35 as a region of interest. A positional cloning effort to identify a balanced 1p35 translocation found in a Wilms tumor has led to the isolation of a YAC, crossing this breakpoint.

Original languageEnglish (US)
Pages (from-to)490-494
Number of pages5
JournalMedical and Pediatric Oncology
Volume27
Issue number5
DOIs
StatePublished - Nov 1996

Keywords

  • Beckwith-Wiedemann syndrome
  • childhood tumors
  • chromosome 11p
  • chromosome 1p
  • hemihypertrophy
  • positional cloning

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Oncology
  • Cancer Research

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