IRF2BPL: A new genotype for progressive myoclonus epilepsies

The progressive myoclonus epilepsies (PMEs) are a heterogeneous group of neurodegenerative disorders, typically presenting in late childhood. An etiologic diagnosis is achieved in about 80% of patients with PME, and genome-wide molecular studies on remaining, well-selected, undiagnosed cases can further dissect the underlying genetic heterogeneity. Through whole-exome sequencing (WES), we identified pathogenic truncating variants in the IRF2BPL gene in two, unrelated patients presenting with PME. IRF2BPL belongs to the transcriptional regulators family and it is expressed in multiple human tissues, including the brain. Recently missense and nonsense mutations in IRF2BPL were found in patients presenting with developmental delay and epileptic encephalopathy, ataxia, and movement disorders, but none with clear PME. We identified 13 other patients in the literature with myoclonic seizures and IRF2BPL variants. There was no clear genotype-phenotype correlation. With the description of these cases, the IRF2BPL gene should be considered in the list of genes to be tested in the presence of PME, in addition to patients with neurodevelopmental or movement disorders.

Automated summary

Progressive myoclonus epilepsies (PMEs) are a diverse group of neurodegenerative disorders that typically occur in late childhood. Through genome-wide molecular studies, pathogenic variants in the IRF2BPL gene were identified in patients with PME, suggesting its involvement in the disease. These findings expand the phenotypic spectrum of IRF2BPL-related disorders and highlight the importance of considering this gene in the diagnosis of patients with PME.