Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/7342
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Type: Journal article
Title: GABRD encoding a protein for extra- or peri-synaptic GABAA receptors is a susceptibility locus for generalized epilepsies
Author: Dibbens, L.
Feng, H.
Richards, M.
Harkin, L.
Hodgson, B.
Scott, D.
Jenkins, M.
Petrou, S.
Sutherland, G.
Scheffer, I.
Berkovic, S.
Mcdonald, R.
Mulley, J.
Citation: Human Molecular Genetics, 2004; 13(13):1315-1319
Publisher: Oxford Univ Press
Issue Date: 2004
ISSN: 0964-6906
1460-2083
Statement of
Responsibility: 
Leanne M. Dibbens, Hua-Jun Feng, Michaella C. Richards, Louise A. Harkin, Bree L. Hodgson, Darren Scott, Misty Jenkins, Steven Petrou, Grant R. Sutherland, Ingrid E. Scheffer, Samuel F. Berkovic, Robert L. Macdonald and John C. Mulley
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 δ 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 receptor current amplitudes. As GABAA receptors mediate neuronal inhibition, the reduced receptor current associated with both variants is likely to be associated with increased neuronal excitability. Since d subunit-containing receptors localize to extra- or peri-synaptic membranes and are thought to be involved in tonic inhibition, our results suggest that alteration of this process may contribute to the common generalized epilepsies.
Keywords: Synaptic Membranes; Humans; Epilepsy, Generalized; Seizures, Febrile; Genetic Predisposition to Disease; Receptors, GABA-A; Amino Acid Substitution; Pedigree; Heterozygote; Homozygote; Multifactorial Inheritance; Point Mutation; Female; Male
Rights: Copyright © Oxford University Press 2004; all rights reserved
RMID: 0020040643
DOI: 10.1093/hmg/ddh146
Appears in Collections:Paediatrics publications

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