Extending the phenotypic spectrum of RBFOX1 deletions: Sporadic focal epilepsy. (15th July 2015)

• Record Type: Journal Article
• Authors: Lal, Dennis; Pernhorst, Katharina; Klein, Karl Martin; Reif, Philipp; Tozzi, Rossana; Toliat, Mohammad R.; Winterer, Georg; Neubauer, Bernd; Nürnberg, Peter; Rosenow, Felix; Becker, Felicitas; Lerche, Holger; Kunz, Wolfram S.; Kurki, Mitja I.; Hoffmann, Per; Becker, Albert J.; Perucca, Emilio; Zara, Federico; Sander, Thomas; Weber, Yvonne G.
• Is Part Of: Epilepsia. Volume 56:issue 9(2015:Sep.)
• Page Start: e129
• Page End: e133
• Publication Date: 2015-07-15
• Subjects: Epilepsy -- Periodicals; 616.853
• DOI: 10.1111/epi.13076
• Languages: English
• ISSNs: 0013-9580

Abstract

<abstract abstract-type="main" id="epi13076-abs-0001"> <title>Summary</title> <p>Partial deletions of the <italic>RBFOX1</italic> 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 <italic>RBFOX1</italic> 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 <italic>RBFOX1</italic> 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 <italic>RBFOX1</italic> 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 <italic>RBFOX1</italic> deletions as a risk factor for focal epilepsy and suggests that exonic <italic>RBFOX1</italic> deletions are involved in the broad spectrum of focal and generalized epilepsies.</p> </abstract>