PUBLICATION
De novo variants of IRF2BPL result in developmental epileptic disorder
- Authors
- Wang, Y., Ke, Z., Li, Y., Qiu, M., Liu, J., Yang, Z., Wen, S., Liang, M., Chen, S.
- ID
- ZDB-PUB-240314-12
- Date
- 2024
- Source
- Orphanet journal of rare diseases 19: 121121 (Journal)
- Registered Authors
- Keywords
- IRF2BPL, Epilepsy, Neurodevelopmental disorder, Variant, Zebrafish
- MeSH Terms
-
- Animals
- Carrier Proteins/genetics
- Epilepsy*/diagnosis
- Epilepsy*/genetics
- Humans
- Mutation
- Neurodevelopmental Disorders*/genetics
- Nuclear Proteins/genetics
- Seizures
- Zebrafish/genetics
- PubMed
- 38481258 Full text @ Orphanet J Rare Dis
Citation
Wang, Y., Ke, Z., Li, Y., Qiu, M., Liu, J., Yang, Z., Wen, S., Liang, M., Chen, S. (2024) De novo variants of IRF2BPL result in developmental epileptic disorder. Orphanet journal of rare diseases. 19:121121.
Abstract
Background Pathogenic variants of the IRF2BPL gene have been reported to cause neurodevelopmental disorders; however, studies focused on IRF2BPL in zebrafish are limited.
Results We reported three probands diagnosed with developmental delay and epilepsy and investigated the role of IRF2BPL in neurodevelopmental disorders in zebrafish. The clinical and genetic characteristics of three patients with neurodevelopmental disorder with regression, abnormal movements, loss of speech and seizures (NEDAMSS) were collected. Three de novo variants (NM_024496.4: c.1171 C > T, p.Arg391Cys; c.1157 C > T, p.Thr386Met; and c.273_307del, p.Ala92Thrfs*29) were detected and classified as pathogenic or likely pathogenic according to ACMG guidelines. Zebrafish crispants with disruption of the ortholog gene irf2bpl demonstrated a reduced body length and spontaneous ictal-like and interictal-like discharges in an electrophysiology study. After their spasms were controlled, they gain some development improvements.
Conclusion We contribute two new pathogenic variants for IRF2BPL related developmental epileptic disorder which provided evidences for genetic counseling. In zebrafish model, we for the first time confirm that disruption of irf2bpl could introduce spontaneous electrographic seizures which mimics key phenotypes in human patients. Our follow-up results suggest that timely cessation of spasmodic seizures can improve the patient's neurodevelopment.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping