GRIN2A mutations cause epilepsy-aphasia spectrum disorders

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

300 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1073-1076
Number of pages4
JournalNature Genetics
Issue number9
StatePublished - Sep 2013

ASJC Scopus subject areas

  • Genetics


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