Fig. 2.

Hypothesised model of the effect of premature transcription termination of KCNQ1 on the methylation status of the IC2 (figure modified from Valente et al. [21]). In healthy individuals, IC2 is methylated on the maternal allele (indicated by a filled lollipop) leading to an expression of KCNQ1 and a repression of KCNQ1OT1. On the unmethylated paternal allele (indicated by an open lollipop), KCNQ1 is repressed but KCNQ1OT1 is expressed. Active promoters and transcription are indicated by bent black arrows, and correct transcription of KCNQ1 is depicted by a curved dark green line. The curved light green line indicates the paternal transcription of KCNQ1 in the heart. Due to a variant in KCNQ1, the transcription of KCNQ1 is disturbed (indicated by a red cross). After maternal transmission, the variant leads to BWS due to the LOM of IC2 and, due to haploinsufficiency of KCNQ1, to LQTS. After paternal transmission, the variant may lead to isolated LQTS due to the haploinsufficiency of KCNQ1