+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

RBFOX1 and RBFOX3 mutations in rolandic epilepsy

RBFOX1 and RBFOX3 mutations in rolandic epilepsy

Plos One 8(9): E73323-E73323

Partial deletions of the gene encoding the neuronal splicing regulator RBFOX1 have been reported in a range of neurodevelopmental diseases, including idiopathic generalized epilepsy. The RBFOX1 protein and its homologues (RBFOX2 and RBFOX3) regulate alternative splicing of many neuronal transcripts involved in the homeostatic control of neuronal excitability. In this study, we explored if structural microdeletions and exonic sequence variations in RBFOX1, RBFOX2, RBFOX3 confer susceptibility to rolandic epilepsy (RE), a common idiopathic focal childhood epilepsy. By high-density SNP array screening of 289 unrelated RE patients, we identified two hemizygous deletions, a 365 kb deletion affecting two untranslated 5'-terminal exons of RBFOX1 and a 43 kb deletion spanning exon 3 of RBFOX3. Exome sequencing of 242 RE patients revealed two novel probably deleterious variants in RBFOX1, a frameshift mutation (p.A233Vfs*74) and a hexanucleotide deletion (p.A299_A300del), and a novel nonsense mutation in RBFOX3 (p.Y287*). Although the three variants were inherited from unaffected parents, they were present in all family members exhibiting the RE trait clinically or electroencephalographically with only one exception. In contrast, no deleterious mutations of RBFOX1 and RBFOX3 were found in the exomes of 6503 non-RE subjects deposited in the Exome Variant Server database. The observed RBFOX3 exon 3 deletion and nonsense mutation suggest that RBFOX3 represents a novel risk factor for RE, indicating that exon deletions and truncating mutations of RBFOX1 and RBFOX3 contribute to the genetic variance of partial and generalized idiopathic epilepsy syndromes.

(PDF emailed within 0-6 h: $19.90)

Accession: 055333641

Download citation: RISBibTeXText

PMID: 24039908

DOI: 10.1371/journal.pone.0073323

Related references

Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes. Nature Genetics 45(9): 1067-1072, 2013

Children with Rolandic spikes and ictal vomiting: Rolandic epilepsy or Panayiotopoulos syndrome?. Epileptic Disorders 5(3): 139-143, 2003

Magnetoencephalographic analysis of rolandic discharges in a patient with rolandic epilepsy associated with oromotor deficits. Journal of Child Neurology 19(6): 456-459, 2004

MEG localization of rolandic spikes with respect to SI and SII cortices in benign rolandic epilepsy. Neuroimage 20(4): 2051-2061, 2003

Generators of rolandic discharges in a patient with a typical benign rolandic epilepsy. Koga, Y, Nagata, K, Hirata, K International Congress Series; Brain topography today 495-501, 1998

Dipole source analysis of rolandic spikes in benign rolandic epilepsy and other clinical syndromes. Brain Topography. 5(3): 203-213, 1993

Dipole modeling of interictal rolandic spikes and median nerve SEPs in children with benign rolandic epilepsy (BREC). Epilepsia 38(10): 1154-1154, 1998

Cognitive deficits in children with benign rolandic epilepsy of childhood or rolandic discharges: a study of children between 4 and 7 years of age with and without seizures compared with healthy controls. Epilepsy & Behavior 16(4): 646-651, 2010

Extending the phenotypic spectrum of RBFOX1 deletions: Sporadic focal epilepsy. Epilepsia 56(9): E129-E133, 2016

Childhood epilepsy with centro-temporal spikes (rolandic epilepsy) and written language. Developmental Medicine and Child Neurology, 2017

Guidelines for discontinuation of antiepileptic drugs for childhood absence epilepsy and rolandic epilepsy. Japanese Journal of Psychiatry and Neurology 48(2): 245-248, 1994

Upregulation of RBFOX1 in the malformed cortex of patients with intractable epilepsy and in cultured rat neurons. International Journal of Molecular Medicine 35(3): 597-606, 2015

Dipole tracing in childhood epilepsy with special reference to rolandic epilepsy. Brain Topography 3(1): 220, 1990

The Epilepsy-Aphasia Spectrum: From Landau-Kleffner Syndrome to Rolandic Epilepsy. Neuropediatrics 48(6): 484-486, 2017

Dipole tracing in childhood epilepsy with special reference to rolandic epilepsy. Brain Topography 4(3): 193-199, 1992