Genetic modifiers affecting severity of epilepsy caused by mutation of sodium channel Scn2a

Sarah K. Bergren, Shu Chen, Andrzej Galecki, Jennifer A. Kearney*

*Corresponding author for this work

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Mutations in the voltage-gated sodium channels SCN1A and SCN2A are responsible for several types of human epilepsy. Variable expressivity among family members is a common feature of these inherited epilepsies, suggesting that genetic modifiers may influence the clinical manifestation of epilepsy. The transgenic mouse model Scn2a Q54 has an epilepsy phenotype as a result of a mutation in Scn2a that slows channel inactivation. The mice display progressive epilepsy that begins with short-duration partial seizures that appear to originate in the hippocampus. The partial seizures become more frequent and of longer duration with age and often induce secondary generalized seizures. Clinical severity of the Scn2a Q54 phenotype is influenced by genetic background. Congenic C57BL/6J.Q54 mice exhibit decreased incidence of spontaneous seizures, delayed seizure onset, and longer survival in comparison with [C57BL/6J x SJL/J]F1.Q54 mice. This observation indicates that strain SJL/J carries dominant modifier alleles at one or more loci that determine the severity of the epilepsy phenotype. Genome-wide interval mapping in an N2 backcross revealed two modifier loci on Chromosomes 11 and 19 that influence the clinical severity of of this sodium channel-induced epilepsy. Modifier genes affecting clinical severity in the Scn2a Q54 mouse model may contribute to the variable expressivity seen in epilepsy patients with sodium channel mutations.

Original languageEnglish (US)
Pages (from-to)683-690
Number of pages8
JournalMammalian Genome
Volume16
Issue number9
DOIs
StatePublished - Sep 1 2005

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Sodium Channels
Epilepsy
Mutation
Seizures
Phenotype
Modifier Genes
Voltage-Gated Sodium Channels
Chromosomes, Human, Pair 19
Chromosomes, Human, Pair 11
Transgenic Mice
Hippocampus
Alleles
Genome
Survival
Incidence

ASJC Scopus subject areas

  • Genetics

Cite this

Bergren, Sarah K. ; Chen, Shu ; Galecki, Andrzej ; Kearney, Jennifer A. / Genetic modifiers affecting severity of epilepsy caused by mutation of sodium channel Scn2a. In: Mammalian Genome. 2005 ; Vol. 16, No. 9. pp. 683-690.
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Genetic modifiers affecting severity of epilepsy caused by mutation of sodium channel Scn2a. / Bergren, Sarah K.; Chen, Shu; Galecki, Andrzej; Kearney, Jennifer A.

In: Mammalian Genome, Vol. 16, No. 9, 01.09.2005, p. 683-690.

Research output: Contribution to journalArticle

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