Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders

Gene: KCNQ1OT1

Green List (high evidence)

from OMIM : In 2 related individuals with Beckwith-Wiedemann syndrome, Niemitz et al. (2004) described 1 case where the deletion was maternally inherited; in the other, it was paternally inherited. In the case of maternal inheritance, the deletion caused BWS with silencing of p57(KIP2) (CDKN1C; 600856), indicating that an element important for the regulation of p57(KIP2) expression had been deleted. When inherited paternally, there was no BWS phenotype, suggesting that the LIT1 RNA itself is not necessary for normal development in humans.

Created: 31 May 2019, 11:38 a.m.

Review and Green rating from Kate Tatton-Brown April 2017. Imprinted rather than LOF

Created: 31 May 2019, 9:37 a.m.

Added tag to explain why there is no Ensembl gene ID for this entity.

Created: 6 Jan 2017, 3:39 p.m.

"Methylation defects in the upstream KvDMR cause disease but not loss of function mutations in KCNQ1OT1. It is conceivable that genetic disruptions on the maternal allele could cause these methylation defects but this is as yet unproven." Comment made by Richard Scott (North Thames GMC/UCL), Oct. 9, 2015, 9:45 p.m.

Created: 29 Mar 2016, 1:34 p.m.

Methylation-specific MLPA (MS-MLPA) of this gene is used to test for Beckwith-Wiedemann syndrome by Emory Genetics Laboratory. Mutational spectrum tested for by the UKGTN: loss of methylation at LIT1 (KCNQ1OT1 is the HGNC-approved symbol for this gene, KvDMR1 within LIT1), Hypermethylation of H19, duplication of paternally inherited 11p15 region, paternal uniparental disomy of 11p15 region, maternal H19 DMR microdeletion, maternal KvDMR1 microdeletion. ICR1 is the H19/IGF2-imprinting control region located in the 11p15.5 region.

Created: 29 Mar 2016, 1:33 p.m.

Comment on list classification: This gene will remain red as pathogenicity is caused by changes to methylation of this gene

Created: 8 Jun 2016, 2:25 p.m.