Mutations in the GABA transporter SLC6A1 cause epilepsy with myoclonic-atonic seizures

Gemma L. Carvill, Jacinta M. McMahon, Amy Schneider, Matthew Zemel, Candace T. Myers, Julia Saykally, John Nguyen, Angela Robbiano, Federico Zara, Nicola Specchio, Oriano Mecarelli, Robert L. Smith, Richard J. Leventer, Rikke S. Møller, Marina Nikanorova, Petia Dimova, Albena Jordanova, Steven Petrou, Ingo Helbig, Pasquale StrianoSarah Weckhuysen, Samuel F. Berkovic, Ingrid E. Scheffer*, Heather C. Mefford

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

147 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)808-815
Number of pages8
JournalAmerican journal of human genetics
Issue number5
StatePublished - May 7 2015

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics


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