Karen Y. Niederhoffer and Maria Peñaherrera Contributed equally to this work.
Article first published online: 21 MAY 2012
Copyright © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 158A, Issue 7, pages 1662–1669, July 2012
How to Cite
Niederhoffer, K. Y., Peñaherrera, M., Pugash, D., Rupps, R., Arbour, L., Tessier, F., Choufani, S., Zhao, C., Manokhina, I., Shuman, C., Robinson, W. P., Weksberg, R. and Boerkoel, C. F. (2012), Beckwith–Wiedemann syndrome in sibs discordant for IC2 methylation. Am. J. Med. Genet., 158A: 1662–1669. doi: 10.1002/ajmg.a.35377
How to Cite this Article: Niederhoffer KY, Peñaherrera M, Pugash D, Rupps R, Arbour L, Tessier F, Choufani S, Zhao C, Manokhina I, Shuman C, Robinson WP, Weksberg R, Boerkoel CF. 2012. Beckwith–Wiedemann syndrome in sibs discordant for IC2 methylation. Am J Med Genet Part A. 158A:1662–1669.
- Issue published online: 18 JUN 2012
- Article first published online: 21 MAY 2012
- Manuscript Accepted: 19 FEB 2012
- Manuscript Received: 28 OCT 2011
- Canadian Institutes for Health Research
- Beckwith–Wiedemann syndrome;
- imprinting, genetic;
- multiple hypomethylation syndrome;
- genetic counseling
Genetically heterogeneous imprinting disorders include Beckwith–Wiedemann syndrome (BWS) and multiple maternal hypomethylation syndrome (MMHS). Using DNA sequencing, quantitative PCR, SNuPE, pyrosequencing, and hybridization to the Illumina GoldenGate Methylation Cancer Panel 1 array, we characterized the genomic DNA of two brothers with BWS who were discordant for loss of methylation at several differentially methylated regions (DMR), including imprinting center 2 (IC2) on chromosome band 11p15.5, which is often hypomethylated in BWS. In keeping with MMHS, the elder child had hypomethylation of SGCE and PLAGL1 as well as of IC2, whereas the younger brother demonstrated no loss of methylation at these DMRs. Although this discordance is consistent with the observation that 15–20% of individuals with BWS do not have detectable genetic or epigenetic alterations of 11p15.5, this is the first report of familial recurrence of BWS with discordance for chromosomal 11p15.5 alterations. We hypothesize that this apparent discordance arises either from mosaicism precluding identification of IC2 hypomethylation in blood or buccal mucosa DNA of the younger child, or from hypomethylation at a site not interrogated by our molecular studies. © 2012 Wiley Periodicals, Inc.