Journal Article

GRIN2A mutations cause epilepsy-aphasia spectrum disorders

Burnashev, Nail, Damiano, John A, Berkovic, Samuel F, Scheffer, Ingrid E, Shendure, Jay, Cook, Joseph, Tsai, Meng-Han, O'Roak, Brian J, Carvill, Gemma L, Geraghty, Eileen, Mefford, Heather C, Lozovaya, Natalia, Ouvrier, Robert, Webster, Richard, Bruneau, Nadine, Hildebrand, Michael S, Turner, Samantha J, Khan, Adiba, Regan, Brigid M, Sadleir, Lynette G, Szepetowski, Pierre, Yendle, Simone C

2013

Overview

Heather Mefford, Ingrid Scheffer and colleagues report the identification of inherited mutations in GRIN2A that cause epilepsy-aphasia syndromes, which have a characteristic EEG pattern and developmental regression affecting language. Epilepsy-aphasia syndromes (EAS) are a group of rare, severe epileptic encephalopathies of unknown etiology with a characteristic electroencephalogram (EEG) pattern and developmental regression particularly affecting language. Rare pathogenic deletions that include GRIN2A have been implicated in neurodevelopmental disorders. We sought to delineate the pathogenic role of GRIN2A in 519 probands with epileptic encephalopathies with diverse epilepsy syndromes. We identified four probands with GRIN2A variants that segregated with the disorder in their families. Notably, all four families presented with EAS, accounting for 9% of epilepsy-aphasia cases. We did not detect pathogenic variants in GRIN2A in other epileptic encephalopathies ( n = 475) nor in probands with benign childhood epilepsy with centrotemporal spikes ( n = 81). We report the first monogenic cause, to our knowledge, for EAS. GRIN2A mutations are restricted to this group of cases, which has important ramifications for diagnostic testing and treatment and provides new insights into the pathogenesis of this debilitating group of conditions.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 692/699/375/178 / Agriculture / Animal Genetics and Genomics / Aphasia / Biomedicine / Cancer Research / Diagnosis / Electroencephalography / Epilepsy / Female / Gene Function / Gene mutations / Genetic aspects / Health aspects / Human Genetics / Humans / Landau-Kleffner Syndrome - diagnosis / Landau-Kleffner Syndrome - genetics / letter / Male / Medical research / Mutation / Pedigree / Phenotype / Receptors, N-Methyl-D-Aspartate - genetics / Risk factors / Studies