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Beygo, J.* ; Bürger, J.* ; Strom, T.M. ; Kaya, S.* ; Buiting, K.*

Disruption of KCNQ1 prevents methylation of the ICR2 and supports the hypothesis that its transcription is necessary for imprint establishment.

Eur. J. Hum. Genet. 27, 903-908 (2019)
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Beckwith-Wiedemann syndrome (BWS; OMIM #130650) is an imprinting disorder caused by genetic or epigenetic alterations of one or both imprinting control regions on chromosome 11p15.5. Hypomethylation of the centromeric imprinting control region (KCNQ1OT1:TSS-DMR, ICR2) is the most common molecular cause of BWS and is present in about half of the cases. Based on a BWS family with a maternal deletion of the 5' part of KCNQ1 we have recently hypothesised that transcription of KCNQ1 is a prerequisite for the establishment of methylation at the KCNQ1OT1:TSS-DMR in the oocyte. Further evidence for this hypothesis came from a mouse model where methylation failed to be established when a poly(A) truncation cassette was inserted into this locus to prevent transcription through the DMR. Here we report on a family where a balanced translocation disrupts the KCNQ1 gene in intron 9. Maternal inheritance of this translocation is associated with hypomethylation of the KCNQ1OT1:TSS-DMR and BWS. This finding strongly supports our previous hypothesis that transcription of KCNQ1 is required for establishing the maternal methylation imprint at the KCNQ1OT1:TSS-DMR.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Beckwith-wiedemann Syndrome; Copy Number Variations; Long-qt Syndrome; Diagnosis; Deletion; Region; Gene
ISSN (print) / ISBN 1018-4813
e-ISSN 1476-5438
Quellenangaben Volume: 27, Issue: 6, Pages: 903-908 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place Macmillan Building, 4 Crinan St, London N1 9xw, England
Reviewing status Peer reviewed