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

Gene: KCNQ1OT1

Amber List (moderate evidence)

KCNQ1OT1 (KCNQ1 opposite strand/antisense transcript 1 (non-protein coding))
EnsemblGeneIds (GRCh38): ENSG00000269821
EnsemblGeneIds (GRCh37): ENSG00000269821
OMIM: 604115, Gene2Phenotype
KCNQ1OT1 is in 3 panels

3 reviews

Louise Daugherty (Genomics England Curator)

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.

Ellen McDonagh (Genomics England Curator)

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.

Sarah Leigh (Genomics England Curator)

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.

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Sources
  • Emory Genetics Laboratory
  • UKGTN
Phenotypes
  • Beckwith-Wiedemann Syndrome, 130650
Tags
locus-type-rna-long-non-coding
OMIM
604115
Clinvar variants
Variants in KCNQ1OT1
Penetrance
Complete
Publications
Mode of Pathogenicity
Other - please provide details in the comments
Panels with this gene

History Filter Activity

31 May 2019, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: kcnq1ot1 has been classified as Amber List (Moderate Evidence).

31 May 2019, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: KCNQ1OT1 were changed from Beckwith-Wiedemann Syndrome to Beckwith-Wiedemann Syndrome, 130650

31 May 2019, Gel status: 2

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene: KCNQ1OT1 was changed from Other - please specifiy in evaluation comments to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)

31 May 2019, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: kcnq1ot1 has been classified as Amber List (Moderate Evidence).

31 May 2019, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: KCNQ1OT1 were set to PMID: 12949703

8 Jun 2016, Gel status: 1

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

29 Mar 2016, Gel status: 1

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

29 Mar 2016, Gel status: 1

Set mode of pathogenicity

Ellen McDonagh (Genomics England Curator)

Mode of pathogenicity for KCNQ1OT1 was changed to Other - please provide details in the comments

29 Mar 2016, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

KCNQ1OT1 was added to Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorderspanel. Sources: UKGTN,Emory Genetics Laboratory,Expert Review Red

29 Mar 2016, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

KCNQ1OT1 was created by ellenmcdonagh