Truncation of the GABAA-Receptor γ2 Subunit in a Family with Generalized Epilepsy with Febrile Seizures Plus

Recent findings from studies of two families have shown that mutations in the GABA A -receptor γ2 subunit are associated with generalized epilepsies and febrile seizures. Here we describe a family that has generalized epilepsy with febrile seizures plus (GEFS + ), including an individual with severe...

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Bibliographic Details
Published in:American journal of human genetics 2001-12, Vol.70 (2), p.530-536
Main Authors: Harkin, Louise A., Bowser, David N., Dibbens, Leanne M., Singh, Rita, Phillips, Fiona, Wallace, Robyn H., Richards, Michaella C., Williams, David A., Mulley, John C., Berkovic, Samuel F., Scheffer, Ingrid E., Petrou, Steven
Format: Article
Language:English
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Summary:Recent findings from studies of two families have shown that mutations in the GABA A -receptor γ2 subunit are associated with generalized epilepsies and febrile seizures. Here we describe a family that has generalized epilepsy with febrile seizures plus (GEFS + ), including an individual with severe myoclonic epilepsy of infancy, in whom a third GABA A -receptor γ2-subunit mutation was found. This mutation lies in the intracellular loop between the third and fourth transmembrane domains of the GABA A -receptor γ2 subunit and introduces a premature stop codon at Q351 in the mature protein. GABA sensitivity in Xenopus laevis oocytes expressing the mutant γ2 Q351X subunit is completely abolished, and fluorescent-microscopy studies have shown that receptors containing GFP-labeled γ2 Q351X protein are retained in the lumen of the endoplasmic reticulum. This finding reinforces the involvement of GABA A receptors in epilepsy.
ISSN:0002-9297
1537-6605