Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/27571
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Type: Journal article
Title: Susceptibility genes for complex epilepsy
Author: Mulley, J.
Scheffer, I.
Harkin, L.
Berkovic, S.
Dibbens, L.
Citation: Human Molecular Genetics, 2005; 14(SI Sp. Iss. 2):R243-R249
Publisher: Oxford Univ Press
Issue Date: 2005
ISSN: 0964-6906
1460-2083
Statement of
Responsibility: 
John C. Mulley, Ingrid E. Scheffer, Louise A. Harkin, Samuel F. Berkovic and Leanne M. Dibbens
Abstract: Common idiopathic epilepsies are, clinically and genetically, a heterogeneous group of complex seizure disorders. Seizures arise from periodic neuronal hyperexcitability of unknown cause. The genetic component is mostly polygenic, where each susceptibility gene in any given individual is likely to represent a small component of the total heritability. Two susceptibility genes have been so far identified, where genetic variation is associated with experimentally demonstrated changes in ion channel properties, consistent with seizure susceptibility. Rare variants and a polymorphic allele of the T-type calcium channel CACNA1H and a polymorphic allele and a rare variant of the GABA(A) receptor delta subunit gene have differential functional effects. We speculate that these and other as yet undiscovered susceptibility genes for complex epilepsy could act as 'modifier' loci, affecting penetrance and expressivity of the mutations of large effect in those 'monogenic' epilepsies with simple inheritance that segregate through large families. Discovery of epilepsy-associated ion channel defects in these rare families has opened the door to the discovery of the first two susceptibility genes in epilepsies with complex genetics. The susceptibility genes so far detected are not commonly involved in complex epilepsy suggesting the likelihood of considerable underlying polygenic heterogeneity.
Keywords: Humans; Epilepsy; Genetic Predisposition to Disease; Ion Channels; Calcium Channels, T-Type; Receptors, GABA-A; Multifactorial Inheritance; Alleles; Models, Genetic; Genetic Variation
Description: Copyright © The Author 2005. Published by Oxford University Press. All rights reserved.
RMID: 0020051208
DOI: 10.1093/hmg/ddi355
Appears in Collections:Molecular and Biomedical Science publications

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