Mutations in the GABA Transporter SLC6A1 Cause Epilepsy with Myoclonic-Atonic Seizures
| Autor: | Rikke S. Møller, Julia Saykally, Ingo Helbig, John Nguyen, Nicola Specchio, Jacinta M McMahon, Oriano Mecarelli, Matthew Zemel, Samuel F. Berkovic, Marina Nikanorova, Heather C. Mefford, Federico Zara, R Smith, Gemma L. Carvill, Amy L Schneider, Sarah Weckhuysen, Ingrid E. Scheffer, Angela Robbiano, Richard J. Leventer, Steven Petrou, Candace T. Myers, Petia Dimova, Pasquale Striano, Albena Jordanova |
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| Přispěvatelé: | EuroEPINOMICS Rare Epilepsy Syndro |
| Rok vydání: | 2015 |
| Předmět: |
GABA Plasma Membrane Transport Proteins
Male Epilepsies Myoclonic Pharmacology Epilepsies medicine.disease_cause Synapse Epilepsy Mice Report medicine Myoclonic atonic seizures Genetics GABA transporter Missense mutation Animals Humans Genetic Predisposition to Disease Genetics(clinical) Generalized epilepsy Genetics (clinical) Mutation biology Generalized Epilepsy Generalized High-Throughput Nucleotide Sequencing medicine.disease biology.protein Human medicine Myoclonic |
| Zdroj: | Carvill, G L, McMahon, J M, Schneider, A, Zemel, M, Myers, C T, Saykally, J, Nguyen, J, Robbiano, A, Zara, F, Specchio, N, Mecarelli, O, Smith, R L, Leventer, R J, Møller, R S, Nikanorova, M, Dimova, P, Jordanova, A, Petrou, S, Helbig, I, Striano, P, Weckhuysen, S, Berkovic, S F, Scheffer, I E, Mefford, H C & EuroEPINOMICS Rare Epilepsy Syndrome Myoclonic-Astatic Epilepsy & Dravet working group 2015, ' Mutations in the GABA Transporter SLC6A1 Cause Epilepsy with Myoclonic-Atonic Seizures ', American Journal of Human Genetics, vol. 96, no. 5, pp. 808-815 . https://doi.org/10.1016/j.ajhg.2015.02.016 The American journal of human genetics |
| ISSN: | 0002-9297 |
| DOI: | 10.1016/j.ajhg.2015.02.016 |
| Popis: | GAT-1, encoded by SLC6A1, is one of the major gamma-aminobutyric acid (GABA) transporters in the brain and is responsible for re-uptake of GABA from the synapse. In this study, targeted resequencing of 644 individuals with epileptic encephalopathies led to the identification of six SLC6A1 mutations in seven individuals, all of whom have epilepsy with myoclonic-atonic seizures (MAE). We describe two truncations and four missense alterations, all of which most likely lead to loss of function of GAT-1 and thus reduced GABA re-uptake from the synapse. These individuals share many of the electrophysiological properties of Gat1-deficient mice, including spontaneous spike-wave discharges. Overall, pathogenic mutations occurred in 6/160 individuals with MAE, accounting for similar to 4% of unsolved MAE cases. |
| Databáze: | OpenAIRE |
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