Journal article
GABRD encoding a protein for extra- or peri- synaptic GABAA receptors is susceptibility locus for generalized epilepsies
LM Dibbens, HJ Feng, MC Richards, LA Harkin, BL Hodgson, D Scott, M Jenkins, S Petrou, GR Sutherland, IE Scheffer, SF Berkovic, RL Macdonald, JC Mulley
Human Molecular Genetics | OXFORD UNIV PRESS | Published : 2004
DOI: 10.1093/hmg/ddh146
Abstract
A major challenge in understanding complex idiopathic generalized epilepsies has been the characterization of their underlying molecular genetic basis. Here, we report that genetic variation within the GABRD gene, which encodes the GABAA receptor 8 subunit, affects GABA current amplitude consistent with a model of polygenic susceptibility to epilepsy in humans. We have found a GABRD Glu177Ala variant which is heterozygously associated with generalized epilepsy with febrile seizures plus. We also report an Arg220His allele in GABRD which is present in the general population. Compared with wild-type receptors, α1β2Sδ GABAA receptors containing δ Glu177Ala or Arg220His have decreased GABAA rece..
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