Truncation of the GABA(A)-receptor gamma2 subunit in a family with generalized epilepsy with febrile seizures plus.

Abstract

Recent findings from studies of two families have shown that mutations in the GABA(A)-receptor gamma2 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 gamma2-subunit mutation was found. This mutation lies in the intracellular loop between the third and fourth transmembrane domains of the GABA(A)-receptor gamma2 subunit and introduces a premature stop codon at Q351 in the mature protein. GABA sensitivity in Xenopus laevis oocytes expressing the mutant gamma2(Q351X) subunit is completely abolished, and fluorescent-microscopy studies have shown that receptors containing GFP-labeled gamma2(Q351X) protein are retained in the lumen of the endoplasmic reticulum. This finding reinforces the involvement of GABA(A) receptors in epilepsy.

• Authors: Louise A Harkin, David N Bowser, Leanne M Dibbens, Rita Singh, Fiona Phillips, Robyn H Wallace, Michaella C Richards, David A Williams, John C Mulley, Samuel F Berkovic, Ingrid E Scheffer, Steven Petrou
• Journal: American journal of human genetics (Am J Hum Genet) Vol. 70 Issue 2 Pg. 530-6 (Feb 2002) ISSN: 0002-9297 [Print] United States
• PMID: 11748509 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Codon, Terminator
• Protein Subunits
• Receptors, GABA-A
• gamma-Aminobutyric Acid

Topics

• Animals
• Base Sequence
• Cell Line
• Codon, Terminator (genetics)
• Electrophysiology
• Endoplasmic Reticulum (metabolism)
• Epilepsies, Myoclonic (complications, genetics)
• Epilepsy, Generalized (complications, genetics)
• Female
• Humans
• Male
• Models, Molecular
• Oocytes (drug effects, metabolism)
• Pedigree
• Protein Conformation
• Protein Subunits
• Receptors, GABA-A (chemistry, genetics, metabolism)
• Seizures, Febrile (complications, genetics)
• Sequence Deletion (genetics)
• Xenopus laevis
• gamma-Aminobutyric Acid (pharmacology)