Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• American journal of human genetics, 2015-05, Vol.96 (5), p.808-815

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• GAT-1, encoded by SLC6A1, is one of the major GABA transporters in the brain 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 mutations in SLC6A1 in seven individuals. All presented with the syndrome of epilepsy with myoclonic-atonic seizures (MAE). We describe two truncations and four missense alterations, all 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.