title: A novel locus for idiopathic generalized epilepsy in French-Canadian families maps to 10p11.
abstract: Idiopathic generalized epilepsy (IGE) has evidence of a strong genetic etiology. We conducted genomewide linkage analysis for genes responsible for familial IGE in French-Canadian pedigrees. Twenty families segregating autosomal dominant epilepsy were collected. Four larger IGE families sufficiently powerful for independent linkage analysis were genome-scanned and follow-up fine mapping was performed over regions with LOD scores >3.0. The genotyping of 16 smaller families was carried out at significantly linked loci for supportive linkage analysis and haplotype comparisons. One of the four families provided a significant linkage result at marker D10S1426 on chromosome 10 (two-point LOD score = 3.05, theta = 0, multipoint LOD score = 3.18). Fine mapping revealed a segregating haplotype and key recombination breakpoints, suggesting a candidate gene interval of 6.5 Mb. Multipoint linkage analyses using the additional 16 families yielded a maximum LOD score under heterogeneity of 4.23 (alpha = 0.34) at this locus. Evaluation of recombination breakpoints in these families narrowed the candidate region to 1.7 Mb. Sequencing of the two known genes in this region, NRP1 and PARD3, was negative for mutation. Replication of linkage to this locus in other cohorts of IGE families is essential to characterize the underlying genetic mechanism for the disease.
authors.affiliation: Centre for the Study of Brain Diseases, University of Montreal, Montreal, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Kinirons
authors.forename: Dominique J
authors.initials: DJ
authors.lastname: Verlaan
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Dubé
authors.forename: Josée
authors.initials: J
authors.lastname: Poirier
authors.forename: Charles
authors.initials: C
authors.lastname: Deacon
authors.forename: Anne
authors.initials: A
authors.lastname: Lortie
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Clément
authors.forename: Richard
authors.initials: R
authors.lastname: Desbiens
authors.forename: Lionel
authors.initials: L
authors.lastname: Carmant
authors.forename: Cecile
authors.initials: C
authors.lastname: Cieuta-Walti
authors.forename: Michael
authors.initials: M
authors.lastname: Shevell
authors.forename: Guy A
authors.initials: GA
authors.lastname: Rouleau
authors.forename: Patrick
authors.initials: P
authors.lastname: Cossette
mesh_terms: D002170:Canada; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D004829:Epilepsy, Generalized / Q000235:genetics*; D005260:Female; D005602:France / Q000208:ethnology; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D008126:Lod Score; D008297:Male
chemical_list: D005819:Genetic Markers