Abstract
Beckwith–Wiedemann syndrome (BWS; OMIM #130650) is an overgrowth syndrome caused by different genetic or epigenetic alterations affecting imprinted regions on chromosome 11p15.5. Here we report a family with multiple offspring affected with BWS including giant omphalocoeles in which maternal transmission of a chromosomal rearrangement including an inversion and two deletions leads to hypomethylation of the imprint control region 2 (ICR2). As the deletion includes the promoter and 5′ part of the KCNQ1 gene, we suggest that transcription of this gene may be involved in establishing the maternal methylation imprint of the ICR2, which is located in intron 10 of KCNQ1.
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Acknowledgements
We are grateful to the family for their participation in the study, Dagmar Wieczorek for initiating WGS, Nuria Brämswig for her help regarding the WGS data and Sabine Kaya, Melanie Heitmann and Christina Lich for expert technical assistance. This work was funded by the Bundesministerium für Bildung und Forschung (BMBF; Imprinting diseases, Grant No. 01GM1513A and D).
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Beygo, J., Joksic, I., Strom, T. et al. A maternal deletion upstream of the imprint control region 2 in 11p15 causes loss of methylation and familial Beckwith–Wiedemann syndrome. Eur J Hum Genet 24, 1280–1286 (2016). https://doi.org/10.1038/ejhg.2016.3
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DOI: https://doi.org/10.1038/ejhg.2016.3
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