Human Molecular Genetics, 2002, Vol. 11, No. 11 1317-1325
© 2002 Oxford University Press
Discordant KCNQ1OT1 imprinting in sets of monozygotic twins discordant for Beckwith–Wiedemann syndrome
1Division of Clinical and Metabolic Genetics and the Research Institute, 2Department of Paediatrics and 3Department of Paediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Ontario, Canada, 4Department of Molecular and Medical Genetics, 5Institute of Medical Sciences, 6Department of Laboratory Medicine and Pathobiology and 7Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada, 8University of North Dakota, Grand Forks, ND, USA, 9Center for Human Genetics, University of Nebraska Medical Center, Omaha, NE, USA, 10Department of Medical Genetics, Memorial University Newfoundland, St John's, Newfoundland, Canada, 11Division of Genetics, Albert Einstein Medical Center, Philadelphia, PA, USA, 12Department of Genetics and Development, Columbia University, New York, NY, USA and 13Ontario Cancer Institute, Toronto, Ontario, Canada
Received January 28, 2002; Accepted March 15, 2002
Beckwith–Wiedemann syndrome (BWS) presents with visceromegaly, macroglossia, tumor predisposition and other congenital abnormalities, and is usually associated with abnormalities of chromosome 11p15. A number of identical twin pairs, mostly female, have been reported to be discordant for BWS. We show here that the incidence of female monozygotic twins among patients with BWS is dramatically increased over that of the general population. A cluster of imprinted genes within 11p15 is thought to be coordinately regulated via the imprinted expression of KCNQ1OT1, which encodes an untranslated RNA. In skin fibroblasts from five monozygotic twin pairs discordant for BWS, each affected twin had an imprinting defect at KCNQ1OT1 on 11p15, whereas the unaffected twin did not. Five additional monozygotic twin pairs, for whom only blood was available, also displayed an imprinting defect at KCNQ1OT1. It is possible that discordance for BWS in MZ twins is due to unequal splitting of the inner cell mass during twinning, thereby causing differential maintenance of imprinting at KCNQ1OT1. Alternatively, we propose that KCNQ1OT1 is especially vulnerable to a loss of imprinting event, caused by a lack of maintenance DNA methylation at a critical stage of preimplantation development, and that this loss of imprinting predisposes to twinning as well as to discordance for BWS. These data underscore the importance of continued surveillance of children born following assisted reproductive technologies that impact the preimplantation embryo.
* To whom correspondence should be addressed at: Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8. Tel: +1 416 813 6386; Fax: +1 416 813 5345; Email: rweksb{at}sickkids.on.ca
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. L. Martinez-Frias Can our understanding of epigenetics assist with primary prevention of congenital defects? J. Med. Genet., February 1, 2010; 47(2): 73 - 80. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.J. Silber, M. DeRosa, J. Pineda, K. Lenahan, D. Grenia, K. Gorman, and R.G. Gosden A series of monozygotic twins discordant for ovarian failure: ovary transplantation (cortical versus microvascular) and cryopreservation Hum. Reprod., July 1, 2008; 23(7): 1531 - 1537. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S Abu-Amero, D Monk, J Frost, M Preece, P Stanier, and G E Moore The genetic aetiology of Silver-Russell syndrome J. Med. Genet., April 1, 2008; 45(4): 193 - 199. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Bermejo-Alvarez, D. Rizos, D. Rath, P. Lonergan, and A. Gutierrez-Adan Epigenetic differences between male and female bovine blastocysts produced in vitro Physiol Genomics, January 17, 2008; 32(2): 264 - 272. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Philibert, D. Zenaty, L. Lin, S. Soskin, F. Audran, J. Leger, J. C. Achermann, and C. Sultan Mutational analysis of steroidogenic factor 1 (NR5a1) in 24 boys with bilateral anorchia: a French collaborative study Hum. Reprod., December 1, 2007; 22(12): 3255 - 3261. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kobayashi, A. Sato, E. Otsu, H. Hiura, C. Tomatsu, T. Utsunomiya, H. Sasaki, N. Yaegashi, and T. Arima Aberrant DNA methylation of imprinted loci in sperm from oligospermic patients Hum. Mol. Genet., November 1, 2007; 16(21): 2542 - 2551. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P Bakrania, D O Robinson, D J Bunyan, A Salt, A Martin, J A Crolla, A Wyatt, A Fielder, J Ainsworth, A Moore, et al. SOX2 anophthalmia syndrome: 12 new cases demonstrating broader phenotype and high frequency of large gene deletions Br J Ophthalmol, November 1, 2007; 91(11): 1471 - 1476. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Silber and R. G. Gosden Ovarian Transplantation in a Series of Monozygotic Twins Discordant for Ovarian Failure N. Engl. J. Med., March 29, 2007; 356(13): 1382 - 1384. [Full Text] [PDF]
|
|
|
|
|
|
R.G. Gosden, S.A. Treloar, N.G. Martin, L.F. Cherkas, T.D. Spector, M.J. Faddy, and S.J. Silber Prevalence of premature ovarian failure in monozygotic and dizygotic twins Hum. Reprod., February 1, 2007; 22(2): 610 - 615. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Sato, E. Otsu, H. Negishi, T. Utsunomiya, and T. Arima Aberrant DNA methylation of imprinted loci in superovulated oocytes Hum. Reprod., January 1, 2007; 22(1): 26 - 35. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S Rossignol, V Steunou, C Chalas, A Kerjean, M Rigolet, E Viegas-Pequignot, P Jouannet, Y Le Bouc, and C Gicquel The epigenetic imprinting defect of patients with Beckwith--Wiedemann syndrome born after assisted reproductive technology is not restricted to the 11p15 region J. Med. Genet., December 1, 2006; 43(12): 902 - 907. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y Mineharu, K Takenaka, H Yamakawa, K Inoue, H Ikeda, K-I Kikuta, Y Takagi, K Nozaki, N Hashimoto, and A Koizumi Inheritance pattern of familial moyamoya disease: autosomal dominant mode and genomic imprinting J. Neurol. Neurosurg. Psychiatry, September 1, 2006; 77(9): 1025 - 1029. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Boklage Embryogenesis of chimeras, twins and anterior midline asymmetries Hum. Reprod., March 1, 2006; 21(3): 579 - 591. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Vassart and J. E. Dumont Thyroid Dysgenesis: Multigenic or Epigenetic ... or Both? Endocrinology, December 1, 2005; 146(12): 5035 - 5037. [Full Text] [PDF]
|
|
|
|
 |
|
 M. F. Fraga, E. Ballestar, M. F. Paz, S. Ropero, F. Setien, M. L. Ballestar, D. Heine-Suner, J. C. Cigudosa, M. Urioste, J. Benitez, et al. From The Cover: Epigenetic differences arise during the lifetime of monozygotic twins PNAS, July 26, 2005; 102(30): 10604 - 10609. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H.C. Wong, I. I. Gottesman, and A. Petronis Phenotypic differences in genetically identical organisms: the epigenetic perspective Hum. Mol. Genet., April 15, 2005; 14(suppl_1): R11 - R18. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. van Heyningen and P. L. Yeyati Mechanisms of non-Mendelian inheritance in genetic disease Hum. Mol. Genet., October 1, 2004; 13(suppl_2): R225 - R233. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. W. Mann, S. S. Lee, A. S. Doherty, R. I. Verona, L. D. Nolen, R. M. Schultz, and M. S. Bartolomei Selective loss of imprinting in the placenta following preimplantation development in culture Development, August 1, 2004; 131(15): 3727 - 3735. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Lucifero, J.R. Chaillet, and J. M. Trasler Potential significance of genomic imprinting defects for reproduction and assisted reproductive technology Hum. Reprod. Update, January 1, 2004; 10(1): 3 - 18. [Abstract] [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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
P M H West, D R Love, P M Stapleton, and I M Winship Paternal uniparental disomy in monozygotic twins discordant for hemihypertrophy J. Med. Genet., March 1, 2003; 40(3): 223 - 226. [Full Text] [PDF]
|
|
|
|
|
|
E R Maher, L A Brueton, S C Bowdin, A Luharia, W Cooper, T R Cole, F Macdonald, J R Sampson, C L Barratt, W Reik, et al. Beckwith-Wiedemann syndrome and assisted reproduction technology (ART) J. Med. Genet., January 1, 2003; 40(1): 62 - 64. [Full Text] [PDF]
|
|