| Literature DB >> 25865495 |
Gemma L Carvill1, Jacinta M McMahon2, Amy Schneider2, Matthew Zemel1, Candace T Myers1, Julia Saykally1, John Nguyen1, Angela Robbiano3, Federico Zara3, Nicola Specchio4, Oriano Mecarelli5, Robert L Smith6, Richard J Leventer7, Rikke S Møller8, Marina Nikanorova9, Petia Dimova10, Albena Jordanova11, Steven Petrou12, Ingo Helbig13, Pasquale Striano14, Sarah Weckhuysen15, Samuel F Berkovic2, Ingrid E Scheffer16, Heather C Mefford17.
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.Entities:
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Year: 2015 PMID： 25865495 PMCID： PMC4570550 DOI： 10.1016/j.ajhg.2015.02.016
Source DB: PubMed Journal: Am J Hum Genet ISSN： 0002-9297 Impact factor: 11.025