Journal article

Genetic variants within the second intron of the KCNQ1 gene affect CTCF binding and confer a risk of Beckwith-Wiedemann syndrome upon maternal transmission

Julie Demars, Mansur Ennuri Shmela, Abdul Waheed Khan, Kai Syin Lee, Salah Azzi, Patrice Dehais, Irene Netchine, Sylvie Rossignol, Yves Le Bouc, Assam El-Osta, Christine Gicquel

Journal of Medical Genetics | BMJ PUBLISHING GROUP | Published : 2014


BACKGROUND: Disruption of 11p15 imprinting results in two fetal growth disorders with opposite phenotypes: the Beckwith-Wiedemann (BWS; MIM 130650) and the Silver-Russell (SRS; MIM 180860) syndromes. DNA methylation defects account for 60% of BWS and SRS cases and, in most cases, occur without any identified mutation in a cis-acting regulatory sequence or a trans-acting factor. METHODS: We investigated whether 11p15 cis-acting sequence variants account for primary DNA methylation defects in patients with SRS and BWS with loss of DNA methylation at ICR1 and ICR2, respectively. RESULTS: We identified a 4.5 kb haplotype that, upon maternal transmission, is associated with a risk of ICR2 loss of..

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University of Melbourne Researchers


Awarded by National Health and Medical Research Council of Australia

Funding Acknowledgements

This work was supported by the National Health and Medical Research Council of Australia (Project grant 472637), the Baker IDI Heart and Diabetes Institute, the Victorian Government's Operational Infrastructure Support Program, the Institut National de la Sante et de la Recherche Medicale UMPC -Paris6 funding, ANR EPIFEGRO 2010, Pfizer grant, Agence de Biomedecine 2010 grant. IN is member of the COST Action BM1208. IN and YLB are members of the FP7 ITN Ingenium.