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A novel locus for idiopathic generalized epilepsy in French‐Canadian families maps to 10p11
Author(s) -
Kinirons Peter,
Verlaan Dominique J.,
Dubé MariePierre,
Poirier Josée,
Deacon Charles,
Lortie Anne,
Clément JeanFrançois,
Desbiens Richard,
Carmant Lionel,
CieutaWalti Cecile,
Shevell Michael,
Rouleau Guy A.,
Cossette Patrick
Publication year - 2008
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.32139
Subject(s) - genetics , genetic linkage , pedigree chart , locus (genetics) , haplotype , candidate gene , genotyping , biology , idiopathic generalized epilepsy , genetic heterogeneity , gene mapping , epilepsy , gene , genotype , chromosome , phenotype , neuroscience
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. © 2008 Wiley‐Liss, Inc.