Genome scan of idiopathic generalized epilepsy: Evidence for major susceptibility gene and modifying genes influencing the seizure type

Martina Durner, Mehdi A. Keddache, Livia Tomasini, Shlomo Shinnar, Stanley R. Resor, Jeffrey Cohen, Cynthia Harden, Solomon L. Moshe, David Rosenbaum, Harriet Kang, Karen Ballaban-Gil, Sharon Hertz, Douglas R. Labar, Daniel Luciano, Sibylle Wallace, David Yohai, Irene Klotz, Elisa Dicker, David A. Greenberg

Research output: Contribution to journalArticle

135 Scopus citations

Abstract

Idiopathic generalized epilepsy (IGE) is a common, complex disease with an almost exclusively genetic etiology, but with variable phenotypes. Clinically, IGE can be divided into different syndromes. Varying lines of evidence point to the involvement of several interacting genes in the etiology of IGE. We performed a genome scan in 91 families ascertained through a proband with adolescent-onset IGE. The IGEs included juvenile myoclonic epilepsy (JME), juvenile absence epilepsy (JAE), and epilepsy with generalized tonic clonic seizures (EGTCS). Our linkage results support an oligogenic model for IGE, with strong evidence for a locus common to most IGEs on chromosome 18 (lod score 4.4/5.2 multipoint/two-point) and other loci that may influence specific seizure phenotypes for different IGEs: a previously identified locus on chromosome 6 for JME (lod score 2.5/4.2), a locus on chromosome 8 influencing non-JME forms of IGE (lod score 3.8/2.5), and, more tentatively, two newly discovered loci for absence seizures on chromosome 5 (lod scores 3.812.8 and 3.4/1.9). Our data also suggest that the genetic classification of different forms of IGE is likely to cut across the clinical classification of these subforms of IGE. We hypothesize that interactions of different combinations of these loci produce the related heterogeneous phenotypes seen in IGE families.

Original languageEnglish (US)
Pages (from-to)328-335
Number of pages8
JournalAnnals of Neurology
Volume49
Issue number3
DOIs
StatePublished - Mar 20 2001
Externally publishedYes

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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    Durner, M., Keddache, M. A., Tomasini, L., Shinnar, S., Resor, S. R., Cohen, J., Harden, C., Moshe, S. L., Rosenbaum, D., Kang, H., Ballaban-Gil, K., Hertz, S., Labar, D. R., Luciano, D., Wallace, S., Yohai, D., Klotz, I., Dicker, E., & Greenberg, D. A. (2001). Genome scan of idiopathic generalized epilepsy: Evidence for major susceptibility gene and modifying genes influencing the seizure type. Annals of Neurology, 49(3), 328-335. https://doi.org/10.1002/ana.69