De novo truncating variants in the intronless IRF2BPL are responsible for developmental epileptic encephalopathy

Genetics in Medicine : Official Journal of the American College of Medical Genetics
Frédéric Tran Mau-ThemAntonio Vitobello

Abstract

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. We combined ES analysis and international data sharing. 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 iden...Continue Reading

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Citations

Nov 16, 2019·American Journal of Medical Genetics. Part a·Carlotta SpagnoliCarlo Fusco
Oct 5, 2019·Molecular Biology Reports·Monia GinevrinoEnza Maria Valente
Nov 12, 2020·Seminars in Neurology·David M Ritter, Katherine Holland
Dec 6, 2020·Seizure : the Journal of the British Epilepsy Association·Xiao-Hang QianLi Cao
Jan 29, 2021·Database : the Journal of Biological Databases and Curation·R JorqueraD S Holmes
Aug 28, 2021·International Journal of Molecular Sciences·Luis M ValorRosario Marín
Oct 29, 2021·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Arman ZhaoQin Gu
Nov 21, 2021·Molecular Psychiatry·Anna AlkelaiDavid B Goldstein
Jan 20, 2022·Science Advances·Paul C MarcoglieseHugo J Bellen

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Methods Mentioned

BETA
biopsy

Software Mentioned

GeneMatcher
GeneDx
DECIPHER
ExAC

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