Extending the phenotypic spectrum of RBFOX 1 deletions: Sporadic focal epilepsy
Open accessAbstract
Summary: Partial deletions of the RBFOX 1 gene encoding the neuronal splicing regulator have been reported in a range of neurodevelopmental diseases including idiopathic/genetic generalized epilepsy (IGE/GGE), childhood focal epilepsy, and self‐limited childhood benign epilepsy with centrotemporal spikes (BECTS, rolandic epilepsy), and autism. The protein regulates alternative splicing of many neuronal transcripts involved in the homeostatic control of neuronal excitability. Herein, we examined whether structural deletions affecting RBFOX 1 exons confer susceptibility to common forms of juvenile and adult focal epilepsy syndromes. We screened 807 unrelated patients with sporadic focal epilepsy, and we identified seven hemizygous exonic RBFOX 1 deletions in patients with sporadic focal epilepsy (0.9%) in comparison to one deletion found in 1,502 controls. The phenotypes of the patients carrying RBFOX 1 deletions comprise magnetic resonance imaging (MRI)–negative epilepsy of unknown etiology with frontal and temporal origin (n = 5) and two patients with temporal lobe epilepsy with hippocampal sclerosis. The epilepsies were largely pharmacoresistant but not associated with intellectual disability. Our study extends the phenotypic spectrum of RBFOX 1 deletions as a risk factor for focal epilepsy and suggests that exonic RBFOX 1 deletions are involved in the broad spectrum of focal and generalized epilepsies.
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Human mutations in RBFOX1 have been identified in patients with epilepsy.
“Human mutations in RBFOX1 have been identified in patients with epilepsy126–128”
From The neurogenetics of alternative splicing (2016) · cites this paper as [128]
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- Authors
- Lal, D., Pernhorst, K., Klein, K. M., Reif, P., Tozzi, R., Toliat, M. R., Winterer, G., Neubauer, B., Nürnberg, P., Rosenow, F., Becker, F., Lerche, H., Kunz, W. S., Kurki, M. I., Hoffmann, P., Becker, A. J., Perucca, E., Zara, F., Sander, T., & Weber, Y. G.
- Affiliations
- University of Cologne (DE)
- University of Bonn (DE)
- Philipps University of Marburg (DE)
- Fondazione Istituto Neurologico Nazionale Casimiro Mondino (IT)
- Universitätsklinikum Gießen und Marburg (DE)
- Hertie Institute for Clinical Brain Research (DE)
- Broad Institute (US)
- University of Pavia (IT)
- Istituto Giannina Gaslini (IT)
- Corresponding author
- Weber, Yvonne G.
- ORCID
- Venue
- Epilepsia
- Publisher
- Wiley
- Published
- 2015-07-15
- Volume
- 56
- Issue
- 9
- Pages
- e129-33
- ISSN
- 0013-9580 (ISSN-L)
- 1528-1167
- OpenAlex
- W1724624404
- Cited by
- 40
- References
- 12
- Citations by year
- 2026: 1 · 2024: 4 · 2023: 3 · 2022: 6 · 2021: 3 · 2020: 7 · 2019: 4 · 2018: 3 · 2017: 7 · 2016: 2
- FWCI
- 3.24
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Epilepsia (publishedVersion)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion)
- Funders
- Eisai
- Viropharma
- Italian Medicines Agency
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Keywords
- RBFOX1, focal epilepsy, exon deletion, hemizygous deletion, alternative splicing, neuronal excitability, temporal lobe epilepsy, hippocampal sclerosis, MRI-negative epilepsy, pharmacoresistance, phenotypic spectrum, genetic susceptibility
- MeSH terms
- RNA Splicing Factors, Adolescent, Adult, Child, Child, Preschool, DNA Mutational Analysis, Epilepsies, Partial, Female, Humans, Male, Middle Aged, Phenotype, Meta-Analysis as Topic, RNA-Binding Proteins, Sequence Deletion, Genetic Predisposition to Disease
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