title: Analysis of ELP4, SRPX2, and interacting genes in typical and atypical rolandic epilepsy.
abstract: Rolandic epilepsy (RE) and its atypical variants (atypical rolandic epilepsy, ARE) along the spectrum of epilepsy-aphasia disorders are characterized by a strong but largely unknown genetic basis. Two genes with a putative (ELP4) or a proven (SRPX2) function in neuronal migration were postulated to confer susceptibility to parts of the disease spectrum: the ELP4 gene to centrotemporal spikes and SRPX2 to ARE. To reexamine these findings, we investigated a cohort of 280 patients of European ancestry with RE/ARE for the etiological contribution of these genes and their close interaction partners. We performed next-generation sequencing and single-nucleotide polymorphism (SNP)-array based genotyping to screen for sequence and structural variants. In comparison to European controls we could not detect an enrichment of rare deleterious variants of ELP4, SRPX2, or their interaction partners in affected individuals. The previously described functional p.N327S variant in the X chromosomal SRPX2 gene was detected in two affected individuals (0.81%) and also in controls (0.26%), with some preponderance of male patients. We did not detect an association of SNPs in the ELP4 gene with centrotemporal spikes as previously reported. In conclusion our data do not support a major role of ELP4 and SRPX2 in the etiology of RE/ARE.
authors.affiliation: Department of Neurology, Medical University of Vienna, Vienna, Austria.
authors.forename: Eva M
authors.initials: EM
authors.lastname: Reinthaler
authors.forename: Dennis
authors.initials: D
authors.lastname: Lal
authors.forename: Wiktor
authors.initials: W
authors.lastname: Jurkowski
authors.forename: Martha
authors.initials: M
authors.lastname: Feucht
authors.forename: Hannelore
authors.initials: H
authors.lastname: Steinböck
authors.forename: Ursula
authors.initials: U
authors.lastname: Gruber-Sedlmayr
authors.forename: Gabriel M
authors.initials: GM
authors.lastname: Ronen
authors.forename: Julia
authors.initials: J
authors.lastname: Geldner
authors.forename: Edda
authors.initials: E
authors.lastname: Haberlandt
authors.forename: Birgit
authors.initials: B
authors.lastname: Neophytou
authors.forename: Andreas
authors.initials: A
authors.lastname: Hahn
authors.forename: Janine
authors.initials: J
authors.lastname: Altmüller
authors.forename: Holger
authors.initials: H
authors.lastname: Thiele
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Toliat
authors.forename: Holger
authors.initials: H
authors.lastname: Lerche
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.forename: Thomas
authors.initials: T
authors.lastname: Sander
authors.forename: Bernd A
authors.initials: BA
authors.lastname: Neubauer
authors.forename: Fritz
authors.initials: F
authors.lastname: Zimprich
mesh_terms: D001317:Austria / Q000453:epidemiology; D002170:Canada / Q000453:epidemiology; D002648:Child; D019305:Epilepsy, Rolandic / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: C456976:ELP4 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C116881:SRPX2 protein, human
keywords: Association; CNV; Gene; Idiopathic focal childhood epilepsy; Mutation; SNP