title: Genome-wide linkage scan of epilepsy-related photoparoxysmal electroencephalographic response: evidence for linkage on chromosomes 7q32 and 16p13.
abstract: Photoparoxysmal response (PPR) is an abnormal visual sensitivity of the brain in reaction to intermittent photic stimulation. It is an epilepsy-related electroencephalographic trait with high prevalence in idiopathic epilepsies, especially in common idiopathic generalized epilepsies (IGEs), such as childhood absence epilepsy and juvenile myoclonic epilepsy. This degree of co-morbidity suggests that PPR may be involved in the predisposition to IGE. The identification of genes for PPR would, therefore, aid the dissection of the genetic basis of IGE. Sixteen PPR-multiplex families were collected to conduct a genome-wide linkage scan using broad (all PPR types) and narrow (exclusion of PPR types I and II and the occipital epilepsy cases) models of affectedness for PPR. We found an empirical genome-wide significance for parametric (HLOD) and non-parametric (NPL) linkage (Pgw(HLOD)=0.004 and Pgw(NPL)=0.01) for two respective chromosomal regions, 7q32 at D7S1804 (HLOD=3.47 with alpha=1, P(NPL)=3.39x10(-5)) and 16p13 at D16S3395 (HLOD=2.44 with alpha=1, P(NPL)=7.91x10(-5)). These two genomic regions contain genes that are important for the neuromodulation of cortical dynamics and may represent good targets for candidate-gene studies. Our study identified two susceptibility loci for PPR, which may be related to the underlying myoclonic epilepsy phenotype present in the families studied.
authors.affiliation: Complex Genetics Section, DBG-Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Dalila
authors.initials: D
authors.lastname: Pinto
authors.forename: Birgit
authors.initials: B
authors.lastname: Westland
authors.forename: Gerrit-Jan
authors.initials: GJ
authors.lastname: de Haan
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Rudolf
authors.forename: Berta Martins
authors.initials: BM
authors.lastname: da Silva
authors.forename: Edouard
authors.initials: E
authors.lastname: Hirsch
authors.forename: Dick
authors.initials: D
authors.lastname: Lindhout
authors.forename: Dorothée G A Kasteleijn-Nolst
authors.initials: DG
authors.lastname: Trenité
authors.forename: Bobby P C
authors.initials: BP
authors.lastname: Koeleman
mesh_terms: D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D004832:Epilepsy, Absence / Q000235:genetics*; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D020190:Myoclonic Epilepsy, Juvenile / Q000235:genetics*