A locus for generalized tonic-clonic seizure susceptibility maps to chromosome 10q25-q26.

Journal Article

Inheritance patterns in twins and multiplex families led us to hypothesize that two loci were segregating in subjects with juvenile myoclonic epilepsy (JME), one predisposing to generalized tonic-clonic seizures (GTCS) and a second to myoclonic seizures. We tested this hypothesis by performing genome-wide scan of a large family (Family 01) and used the results to guide analyses of additional families. A locus was identified in Family 01 that was linked to GTCS (10q25-q26). Model-based multipoint analysis of the 10q25-q26 locus showed a logarithm of odds (LOD) score of 2.85; similar results were obtained with model-free analyses (maximum nonparametric linkage [NPL] of 2.71; p = 0.0019). Analyses of the 10q25-q26 locus in 10 additional families assuming heterogeneity revealed evidence for linkage in four families; model-based and model-free analyses showed a heterogeneity LOD (HLOD) of 2.01 (alpha = 0.41) and maximum NPL of 2.56 (p = 0.0027), respectively, when all subjects with GTCS were designated to be affected. Combined analyses of all 11 families showed an HLOD of 4.04 (alpha = 0.51) and maximum NPL score of 4.20 (p = 0.000065). Fine mapping of the locus defined an interval of 4.45Mb. These findings identify a novel locus for GTCS on 10q25-q26 and support the idea that distinct loci underlie distinct seizure types within an epilepsy syndrome such as JME.

Full Text

Duke Authors

Cited Authors

  • Puranam, RS; Jain, S; Kleindienst, AM; Saxena, S; Kim, M-K; Kelly Changizi, B; Padma, MV; Andrews, I; Elston, RC; Tiwari, HK; McNamara, JO

Published Date

  • September 2005

Published In

Volume / Issue

  • 58 / 3

Start / End Page

  • 449 - 458

PubMed ID

  • 16130088

International Standard Serial Number (ISSN)

  • 0364-5134

Digital Object Identifier (DOI)

  • 10.1002/ana.20598

Language

  • eng

Conference Location

  • United States