Back to Search
Start Over
De novo truncating variants in the intronless IRF2BPL are responsible for developmental epileptic encephalopathy
- Source :
- Genetics in Medicine, 21(4), 1008. Lippincott Williams and Wilkins
- Publication Year :
- 2019
-
Abstract
- Purpose: Developmental 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. Methods: We combined ES analysis and international data sharing. Results: We 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. Conclusions: These 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.
- Subjects :
- 0301 basic medicine
Adult
Central Nervous System
Male
Heterozygote
Adolescent
data sharing
030105 genetics & heredity
Biology
developmental epileptic encephalopathies
03 medical and health sciences
Epilepsy
Young Adult
Neurodevelopmental disorder
Seizures
medicine
Transcriptional regulation
Humans
Genetics(clinical)
Child
Gene
Genetics (clinical)
Exome sequencing
Genetics
Genetic heterogeneity
Neurodegeneration
High-Throughput Nucleotide Sequencing
Nuclear Proteins
Electroencephalography
Middle Aged
medicine.disease
030104 developmental biology
Phenotype
Neurodevelopmental Disorders
Mutation
IRF2BPL
Female
Carrier Proteins
exome sequencing
Interferon regulatory factors
Subjects
Details
- Language :
- English
- ISSN :
- 10983600
- Database :
- OpenAIRE
- Journal :
- Genetics in Medicine, 21(4), 1008. Lippincott Williams and Wilkins
- Accession number :
- edsair.doi.dedup.....83b1b30225d1bce3f186d400623a2b18