Truncation of the GABAA-Receptor γ2 Subunit in a Family with Generalized Epilepsy with Febrile Seizures Plus
| Autor: | Steven Petrou, David N. Bowser, Samuel F. Berkovic, Robyn H. Wallace, David A. Williams, Fiona Phillips, Rita Singh, Ingrid E. Scheffer, Louise A. Harkin, John C. Mulley, Leanne M. Dibbens, Michaella C. Richards |
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| Rok vydání: | 2002 |
| Předmět: |
Male
Models Molecular medicine.medical_specialty Protein Conformation Protein subunit Epilepsies Myoclonic Endoplasmic Reticulum Seizures Febrile Cell Line Epilepsy Xenopus laevis SCN1B Internal medicine Report medicine Genetics Animals Humans GABRD Genetics(clinical) Genetics (clinical) gamma-Aminobutyric Acid GABRG2 Sequence Deletion biology Base Sequence GABAA receptor medicine.disease Receptors GABA-A Pedigree Electrophysiology Protein Subunits Endocrinology nervous system biology.protein Codon Terminator Oocytes Myoclonic epilepsy Epilepsy Generalized Female Generalized epilepsy with febrile seizures plus |
| Zdroj: | The American Journal of Human Genetics. 70(2):530-536 |
| ISSN: | 0002-9297 |
| DOI: | 10.1086/338710 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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