Genomic imprinting
Gene: NLRP2Comment on mode of pathogenicity: Maternal NLRP2 variants result in epigenitic disturbance at sites in trans, eg: IC2 in imprinting region at 11p15.5 (PMID 19300480).Created: 29 Apr 2021, 3:08 p.m. | Last Modified: 29 Apr 2021, 3:16 p.m.
Panel Version: 0.101
Comment on list classification: Eamonn Maher (Department of Medical Genetics, University of Cambridge) has recommented a green rating for this gene on this panel. Maternal bialliec variants may result in epigentic distubance of IC2 in imprinting region at 11p15.5 in trans, resulting in Beckwith-Wiedemann syndrome (PMID 19300480) and early embryonic arest, (causing infertility)(PMID 30877238). These findings are supported by a mouse knock out model (PMID 33090377). At least 9 human NLRP2 variants have been identified in families with the above clinical features.Created: 29 Apr 2021, 3:06 p.m. | Last Modified: 29 Apr 2021, 4:20 p.m.
Panel Version: 0.104
Comments from Prof Ian Morison (Department of Pathology, University of Otago) NLRP2 is a component of the subcortical maternal complex. Required for the establishment of imprinting, but not imprinted itself.Created: 2 Feb 2021, 5:35 p.m. | Last Modified: 2 Feb 2021, 5:35 p.m.
Panel Version: 0.84
Not associated with relevant phenotype in OMIM or in Gen2Phen. As a NLRP gene, NLRP2 has epigenetic control of imprinted regions that are part of Multi Locus Imprinting Disturbances.
Review from imprinting expert: A number of patients with IUGR and failure of catch up have an imprinting error (withiin the spectrum of Silver Russell syndrome, temple syndrome) that is caused by variants in NLRP2 in the MOTHER of the patient. Note that LOF mutations (homozygous or heterozygous mutations) identified in the mother would lead to further patient testing for multilocus imprinting disturbance through methylation testing.
Karen Temple (Wessex GMC), 29 Jan 2021Created: 2 Feb 2021, 2:11 p.m. | Last Modified: 29 Apr 2021, 10:44 a.m.
Panel Version: 0.98
Comment on mode of inheritance: The MOI based on review by Karen Temple (Clinical Genetics, University Hospital Southampton NHS Foundation Trust).Created: 2 Feb 2021, 2 p.m. | Last Modified: 2 Feb 2021, 2 p.m.
Panel Version: 0.67
NB: the published evidence base for NLRP2 is currently a single familyhttp://www.imprinting-disorders.eu/?page_id=1112. This is (c) gene whose mutation deranges imprinting in trans.Created: 4 May 2017, 2:37 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Phenotypes
Phenotype resulting from under expression: Beckwith-Wiedemann Syndrome. Multi-locus imprinting disorder; Affected tissue: all
Publications
Phenotypes for gene: NLRP2 were changed from Phenotype resulting from under expression: Beckwith-Wiedemann Syndrome. Multi-locus imprinting disorder; Affected tissue: all to Beckwith-Wiedemann syndrome due to imprinting defect of 11p15 MONDO:0016475
Mode of pathogenicity for gene: NLRP2 was changed from to Other
Gene: nlrp2 has been classified as Green List (High Evidence).
Publications for gene: NLRP2 were set to 19300480; 30221575; 32169557; 28422141; 28317850
Tag watchlist tag was added to gene: NLRP2.
Mode of inheritance for gene: NLRP2 was changed from MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: NLRP2 were set to 19300480; 30221575; 32169557; 28422141
Publications for gene: NLRP2 were set to 19300480; 30221575; 32169557
Publications for gene: NLRP2 were set to PMID: 19300480
NLRP2 was created by ellenmcdonagh
NLRP2 was added to Imprinted Genespanel. Sources: Imprinting GeCIP Subdomain