ArticleGenetics in medicine : official journal of the American College of Medical Genetics2019
De novo truncating variants in the intronless IRF2BPL are responsible for developmental epileptic encephalopathy.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03892798 (Database Of Clinical Data For Individuals With Variants In The IRF2BPL Gene), which is not on this map. Cited by 26 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Database Of Clinical Data For Individuals With Variants In The IRF2BPL Gene
Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Expanding the phenotype of NEDAMSS with a psychiatric perspective: analysis of a new case, and a systematic review of the literature.European child & adolescent psychiatry · 2025Pooled it
- NEDAMSS syndrome-related truncating and missense mutations are associated with aberrant liquid-liquid phase separation of IRF2BPL.Nature communications · 2026Article
- Three pediatric patients with dual rare genetic diagnoses: genetic and clinical findings.American journal of translational research · 2026Article
- Clinical and genetic spectrum of patients with IRF2BPL syndrome.Journal of human genetics · 2025Article
- Clinical characterization of IRF2BPL mutation: Case series and review of the literature.Medicine · 2025Review
- Disorders of puberty and neurodevelopment: A shared etiology?Annals of the New York Academy of Sciences · 2024Review
- Genetic analysis of IRF2BPL in a Taiwanese dystonia cohort: The genotype and phenotype correlation.Annals of clinical and translational neurology · 2024Article
- De novo variants of IRF2BPL result in developmental epileptic disorder.Orphanet journal of rare diseases · 2024Article
- Novel human neurodevelopmental and neurodegenerative disease associated with IRF2BPL gene variants-mechanisms and therapeutic avenues.Frontiers in neuroscience · 2024Review
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- Diagnostic yield and novel candidate genes for neurodevelopmental disorders by exome sequencing in an unselected cohort with microcephaly.BMC genomics · 2023Article
- The current benefit of genome sequencing compared to exome sequencing in patients with developmental or epileptic encephalopathies.Molecular genetics & genomic medicine · 2023Article
- IRF2BPL gene variants with dystonia: one new Chinese case report.BMC neurology · 2023Article
- Novel IRF2BPL gene mutation manifesting as a broad spectrum of neurological disorders: a case report.BMJ neurology open · 2023Article
- Exploring the genetic etiology of drug-resistant epilepsy: incorporation of exome sequencing into practice.Acta neurologica Belgica · 2022Article
- Genetic Testing for Malformations of Cortical Development: A Clinical Diagnostic Study.Neurology. Genetics · 2022Article
- The benefit of diagnostic whole genome sequencing in schizophrenia and other psychotic disorders.Molecular psychiatry · 2022Article
- Loss of IRF2BPL impairs neuronal maintenance through excess Wnt signaling.Science advances · 2022Article
- Molecular Pathogenesis and Peripheral Monitoring of Adult Fragile X-Associated Syndromes.International journal of molecular sciences · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
38 authors at 8 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeDevelopmental and epileptic encephalopathies (DEEs) are severe clinical conditions characterized by stagnation or decline of cognitive and behavioral abilities preceded, accompanied or followed by seizures. Because DEEs are clinically and genetically heterogeneous, next-generation sequencing, especially exome sequencing (ES), is becoming a first-tier strategy to identify the molecular etiologies of these disorders.
methodsWe combined ES analysis and international data sharing.
resultsWe identified 11 unrelated individuals with DEE and de novo heterozygous truncating variants in the interferon regulatory factor 2-binding protein-like gene (IRF2BPL). The 11 individuals allowed for delineation of a consistent neurodevelopmental disorder characterized by mostly normal initial psychomotor development followed by severe global neurological regression and epilepsy with nonspecific electroencephalogram (EEG) abnormalities and variable central nervous system (CNS) anomalies. IRF2BPL, also known as enhanced at puberty protein 1 (EAP1), encodes a transcriptional regulator containing a C-terminal RING-finger domain common to E3 ubiquitin ligases. This domain is required for its repressive and transactivating transcriptional properties. The variants identified are expected to encode a protein lacking the C-terminal RING-finger domain.
conclusionsThese data support the causative role of truncating IRF2BPL variants in pediatric neurodegeneration and expand the spectrum of transcriptional regulators identified as molecular factors implicated in genetic developmental and epileptic encephalopathies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.