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Hum. Reprod. Advance Access published online on December 16, 2005
Human Reproduction, doi:10.1093/humrep/dei405
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© The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received June 14, 2005
Revised October 17, 2005
Accepted October 21, 2005

Article

Assisted reproductive therapies and imprinting disorders--a preliminary British survey

A.G. Sutcliffe 1 *, C.J. Peters 2, S. Bowdin 3, K. Temple 3, W. Reardon 4, L. Wilson 5, J. Clayton-Smith 6, L.A. Brueton 7, W. Bannister 8, and E.R. Maher 9

1 Department of Child Health, Royal Free & University College Medical School, Royal Free Hospital, Lower Ground Floor, Pond Street, London NW3 2PF, UK
2 Department of Child Health, Royal Free & University College Medical School, Royal Free Hospital, London, UK
3 Clinical Genetics Unit, Birmingham Women’s Hospital, University of Birmingham Institute of Biomedical Research, Edgbaston, Birmingham, UK
4 Wessex Clinical Genetics Service and Division of Human Genetics, Southampton University and NHS Trust, Manchester, UK
5 Our Lady’s Hospital for Sick Children, Crumlin, Dublin 12, Ireland
6 Clinical & Molecular Genetics Unit, Institute of Child Health and Great Ormond Street Hospital, London, UK
7 Academic Department of Medical Genetics and Regional Genetic Service, St Mary’s Hospital, Manchester, UK
8 Department of Primary Care and Population Sciences, Royal Free & University College Medical School, London, UK
9 Clinical Genetics Unit, Birmingham Women’s Hospital, University of Birmingham Institute of Biomedical Research, Edgbaston, Birmingham; Section of Medical and Molecular Genetics, University of Birmingham Institute of Biomedical Research, Edgbaston, Birmingham, UK

* To whom correspondence should be addressed.
A.G. Sutcliffe, E-mail: icsi{at}rfc.ucl.ac.uk


  Abstract

BACKGROUND: Recent reports have suggested a higher risk of Beckwith-Wiedemann syndrome (BWS) and Angelman syndrome (AS) after assisted reproductive technologies (ARTs), but it is unclear whether this might also apply to other disorders of genomic imprinting. METHODS: We contacted families of children with BWS, AS, Prader-Willi syndrome (PWS) and transient neonatal diabetes mellitus (TNDM) to determine use of ART. RESULTS: A statistically significant increased frequency of ART in children with BWS was confirmed [2.9%, 95% confidence interval (CI) 1.4-6.3% vs 0.8% expected] but there was no significant association with PWS or TNDM. Consideration of the molecular subgroup of BWS and AS suggested the feasibility of association with ART. CONCLUSIONS: These differences may relate to variations in (i) the molecular mechanisms for disordered imprinting in the different disorders and (ii) the susceptibility of specific imprinting control regions to ART-associated methylation alterations (epimutations).

Keywords: ART/BWS/imprinting/IVF/PWS.
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