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Extending the phenotypic spectrum of RBFOX 1 deletions: Sporadic focal epilepsy
Author(s) -
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.
Publication year - 2015
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.13076
Subject(s) - epilepsy , rolandic epilepsy , hippocampal sclerosis , epilepsy syndromes , generalized epilepsy , idiopathic generalized epilepsy , neuroscience , phenotype , biology , rna splicing , genetics , temporal lobe , gene , rna
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.