Human Molecular Genetics, 2001, Vol. 10, No. 5 467-476
© 2001 Oxford University Press
Increased tumour risk for BWS patients correlates with aberrant H19 and not KCNQ1OT1 methylation: occurrence of KCNQ1OT1 hypomethylation in familial cases of BWS
1Department of Clinical Genetics, 2Department of Anatomy and Embryology, 3Department of Pediatrics and 4Institute for Human Genetics, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands
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.
+ To whom correspondence should be addressed. Tel: +31 205667218; Fax: +31 206918626; Email: m.a.mannens@amc.uva.nl
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D. Lim, S. C. Bowdin, L. Tee, G. A. Kirby, E. Blair, A. Fryer, W. Lam, C. Oley, T. Cole, L. A. Brueton, et al. Clinical and molecular genetic features of Beckwith-Wiedemann syndrome associated with assisted reproductive technologies Hum. Reprod., March 1, 2009; 24(3): 741 - 747. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bruce, K. Hannula-Jouppi, C. M. Lindgren, M. Lipsanen-Nyman, and J. Kere Restriction Site-Specific Methylation Studies of Imprinted Genes with Quantitative Real-Time PCR Clin. Chem., March 1, 2008; 54(3): 491 - 499. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F R Grati, L Turolla, P D'Ajello, A Ruggeri, M Miozzo, G Bracalente, D Baldo, L Laurino, R Boldorini, E Frate, et al. Chromosome 11 segmental paternal isodisomy in amniocytes from two fetuses with omphalocoele: new highlights on phenotype-genotype correlations in Beckwith-Wiedemann syndrome J. Med. Genet., April 1, 2007; 44(4): 257 - 263. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Algar, L. St. Heaps, A. Darmanian, V. Dagar, D. Prawitt, G. B. Peters, and F. Collins Paternally Inherited Submicroscopic Duplication at 11p15.5 Implicates Insulin-like Growth Factor II in Overgrowth and Wilms' Tumorigenesis Cancer Res., March 1, 2007; 67(5): 2360 - 2365. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R H Scott, C A Stiller, L Walker, and N Rahman Syndromes and constitutional chromosomal abnormalities associated with Wilms tumour J. Med. Genet., September 1, 2006; 43(9): 705 - 715. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T Eggermann, N Schonherr, E Meyer, C Obermann, M Mavany, K Eggermann, M B Ranke, and H A Wollmann Epigenetic mutations in 11p15 in Silver-Russell syndrome are restricted to the telomeric imprinting domain J. Med. Genet., July 1, 2006; 43(7): 615 - 616. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N Diaz-Meyer, Y Yang, S N Sait, E R Maher, and M J Higgins Alternative mechanisms associated with silencing of CDKN1C in Beckwith-Wiedemann syndrome J. Med. Genet., August 1, 2005; 42(8): 648 - 655. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Murrell, S. Heeson, W. N. Cooper, E. Douglas, S. Apostolidou, G. E. Moore, E. R. Maher, and W. Reik An association between variants in the IGF2 gene and Beckwith-Wiedemann syndrome: interaction between genotype and epigenotype Hum. Mol. Genet., January 15, 2004; 13(2): 247 - 255. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C Gicquel, J Weiss, J Amiel, V Gaston, Y Le Bouc, and C D Scott Epigenetic abnormalities of the mannose-6-phosphate/IGF2 receptor gene are uncommon in human overgrowth syndromes J. Med. Genet., January 1, 2004; 41(1): e4 - 4. [Full Text] [PDF]
|
|
|
|
|
|
N Diaz-Meyer, C D Day, K Khatod, E R Maher, W Cooper, W Reik, C Junien, G Graham, E Algar, V M Der Kaloustian, et al. Silencing of CDKN1C (p57KIP2) is associated with hypomethylation at KvDMR1 in Beckwith-Wiedemann syndrome J. Med. Genet., November 1, 2003; 40(11): 797 - 801. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Du, L. G. Beatty, W. Zhou, J. Lew, C. Schoenherr, R. Weksberg, and P. D. Sadowski Insulator and silencer sequences in the imprinted region of human chromosome 11p15.5 Hum. Mol. Genet., August 1, 2003; 12(15): 1927 - 1939. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Weksberg, A. C. Smith, J. Squire, and P. Sadowski Beckwith-Wiedemann syndrome demonstrates a role for epigenetic control of normal development Hum. Mol. Genet., April 2, 2003; 12(90001): R61 - 68. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Ishizaki, M. Yoshie, Y. Yaginuma, T. Tanaka, and K. Ogawa Loss of Igf2 Imprinting in Monoclonal Mouse Hepatic Tumor Cells Is Not Associated with Abnormal Methylation Patterns for the H19, Igf2, and Kvlqt1 Differentially Methylated Regions J. Biol. Chem., February 14, 2003; 278(8): 6222 - 6228. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K Pritchard-Jones Controversies and advances in the management of Wilms' tumour Arch. Dis. Child., September 1, 2002; 87(3): 241 - 244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. K. Jones, J. Levorse, and S. M. Tilghman A human H19 transgene exhibits impaired paternal-specific imprint acquisition and maintenance in mice Hum. Mol. Genet., February 1, 2002; 11(4): 411 - 418. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Weksberg, J. Nishikawa, O. Caluseriu, Y.-L. Fei, C. Shuman, C. Wei, L. Steele, J. Cameron, A. Smith, I. Ambus, et al. Tumor development in the Beckwith-Wiedemann syndrome is associated with a variety of constitutional molecular 11p15 alterations including imprinting defects of KCNQ1OT1 Hum. Mol. Genet., December 1, 2001; 10(26): 2989 - 3000. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. John, J. F. -X. Ainscough, S. C. Barton, and M. A. Surani Distant cis-elements regulate imprinted expression of the mouse p57 Kip2 (Cdkn1c) gene: implications for the human disorder, Beckwith-Wiedemann syndrome Hum. Mol. Genet., July 1, 2001; 10(15): 1601 - 1609. [Abstract] [Full Text] [PDF]
|
|