@article{d405f13ee1b94f28904b00f4773081f5,
title = "Mutations in the GABA transporter SLC6A1 cause epilepsy with myoclonic-atonic seizures",
abstract = "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 ∼4% of unsolved MAE cases.",
author = "Carvill, {Gemma L.} and McMahon, {Jacinta M.} and Amy Schneider and Matthew Zemel and Myers, {Candace T.} and Julia Saykally and John Nguyen and Angela Robbiano and Federico Zara and Nicola Specchio and Oriano Mecarelli and Smith, {Robert L.} and Leventer, {Richard J.} and M{\o}ller, {Rikke S.} and Marina Nikanorova and Petia Dimova and Albena Jordanova and Steven Petrou and Ingo Helbig and Pasquale Striano and Sarah Weckhuysen and Berkovic, {Samuel F.} and Scheffer, {Ingrid E.} and Mefford, {Heather C.}",
note = "Funding Information: G.L.C. and I.H. are members of the scientific advisory board of Ambry Genetics. We are grateful to Angelika Ackerhans and Kerstin Wuhlbrandt (Department of Neuropediatrics, University of Kiel) for database and sample management. We appreciate access to phenotypic data on SFARI Base, and we are grateful to all of the families at the participating Simons Simplex Collection (SSC) sites, as well as the principal investigators. This research was supported by the NIH (NINDS 1R01NS069605 to H.C.M.; 1K99NS089858 to G.L.C.), the American Epilepsy Society and the Lennox and Lombroso Fund (G.L.C.), the National Health and Medical Research Council of Australia (S.F.B. and I.E.S.), the Bulgarian Ministry of Education and Science National Science Fund (grant DTK02/67), the Research Fund of the University of Antwerp (grant TOP-BOF-29069 to A.J.). Intramural funds from the University of Kiel and the German Research Foundation (HE5415/5-1 and HE5415/6-1) further supported I.H. Additional funding sources are listed in the Supplemental Data. Publisher Copyright: {\textcopyright} 2015 by The American Society of Human Genetics. All rights reserved.",
year = "2015",
month = may,
day = "7",
doi = "10.1016/j.ajhg.2015.02.016",
language = "English (US)",
volume = "96",
pages = "808--815",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "5",
}