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Intellectual disability

Gene: IRF2BPL

Green List (high evidence)

IRF2BPL (interferon regulatory factor 2 binding protein like)
EnsemblGeneIds (GRCh38): ENSG00000119669
EnsemblGeneIds (GRCh37): ENSG00000119669
OMIM: 611720, Gene2Phenotype
IRF2BPL is in 5 panels

2 reviews

Louise Daugherty (Genomics England Curator)

Comment on phenotypes: added MIMid from OMIM and phenotype data
Created: 31 Oct 2018, 3:31 p.m.
Comment on list classification: New gene suggested by external reviewer and reviewed by curation team. More than three unrelated individuals reported in the literature, ID is part of the phenotype. Publications support gene-disease association and rating of this gene to Green.
Created: 31 Oct 2018, 3:26 p.m.
Comment on publications: Added publication suggested by external reviewer. PMID: 30166628 is a recent publication on IRF2BPL-related phenotypes and reports on 11 unrelated individuals with de novo heterozygous truncating variants. Most individuals displayed complex neurological phenotypes, including delayed psychomotor development, variable Intellectual disability, developmental stagnation or cognitive decline preceded, accompanied or followed by the onset of seizures
Created: 31 Oct 2018, 3:24 p.m.

Konstantinos Varvagiannis (Other)

Green List (high evidence)

PMID: 30166628 is a new publication on the IRF2BPL-related phenotypes and reports on 11 unrelated individuals with de novo heterozygous truncating variants. The reported variants included 6 nonsense and 5 frameshift mutations. Most individuals displayed developmental stagnation or cognitive decline preceded, accompanied or followed by the onset of seizures. Although initial motor development was in most cases normal, mild speech delay was a feature in many individuals while 2 individuals presented with motor and speech delay prior to the onset of regression. In addition, among the 11 individuals, 3 displayed late onset regression (one at 5-6 years, and a further two at 10 and 17 years respectively). Onset of seizures may occur several years after onset of regression. As a result these individuals may be evaluated for their developmental delay and/or regression and the gene could be considered - apart from the epilepsy panel - also for the ID panel. In addition a previous publication (PMID 30057031), suggests a milder phenotype for individuals with missense variants, the latter presenting with developmental delay and seizures without the occurrence of regression. IRF2BPL is an intronless gene. The authors suggest that truncating variants escape nonsense mediated decay, with reverse transcription PCR from patient derived fibroblasts supporting the presence of a translated shorter protein.
Created: 5 Sep 2018, 1:56 a.m.
PMID 30057031 reports on 7 unrelated individuals, all with de novo SNVs in IRF2BPL. Individuals with stopgain SNVs displayed developmental regression, seizures, progressive ataxia and lack of coordination. The phenotype was milder in 2 subjects with missense variants and consisted of hypotonia, global developmental delay and seizures, without motor regression. One of the latter individuals had a diagnosis of autism spectrum disorder (ASD). Many individuals with either type of variant, were non-ambulatory/wheelchair bound and/or non-verbal. Almost all individuals suffered from epilepsy.

Functional analyses in flies were suggestive of a loss-of-function model for IRF2BPL-related disorders.

As the authors point out, individuals with missense and frameshift variants were previously reported by the DDD study [PMID 28135719 - individuals : DDD4K.03622, DDD4K.02435] as well as in a previous ASD study [PMID 25363768 - individuals : 13382 and 11480].
Created: 15 Aug 2018, 10:33 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Global developmental delay; Developmental regression; Seizures; Ataxia

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
Phenotypes
  • Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
  • Global developmental delay, Developmental regression, Seizures, Ataxia
OMIM
611720
Clinvar variants
Variants in IRF2BPL
Penetrance
unknown
Publications
Panels with this gene

History Filter Activity

31 Oct 2018, Gel status: 3

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: IRF2BPL were changed from Global developmental delay; Developmental regression; Seizures; Ataxia to Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures; Global developmental delay, Developmental regression, Seizures, Ataxia

31 Oct 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: irf2bpl has been classified as Green List (High Evidence).

31 Oct 2018, Gel status: 0

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: IRF2BPL were set to 30057031; 28135719; 25363768

15 Aug 2018, Gel status: 0

Added New Source

Konstantinos Varvagiannis (Other)

IRF2BPL was added to Intellectual disability panel. Sources: Literature

15 Aug 2018, Gel status: 0

Created

Konstantinos Varvagiannis (Other)

IRF2BPL was created by Konstantinos Varvagiannis