Journal article

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 Szepetowski Show all

NATURE GENETICS | NATURE PUBLISHING GROUP | Published : 2013

Abstract

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 GRIN..

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Grants

Awarded by US National Institutes of Health (NIH; NINDS)


Awarded by National Health and Medical Research Council of Australia


Awarded by NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE


Funding Acknowledgements

We thank the subjects and their families for participating in our research. H. C. M. is supported by a grant from the US National Institutes of Health (NIH; NINDS 1R01NS069605) and is a recipient of a Burroughs Wellcome Fund Career Award for Medical Scientists. This work was supported by the National Health and Medical Research Council of Australia (Program Grant 628952 to S. F. B. and I. E. S., Practitioner Fellowship 1006110 to I. E. S. and CJ Martin Fellowship (546493) to M. S. H.) and by a Health Research Council of New Zealand project grant to L. G. S. P. S. is supported by ANR (Agence Nationale de la Recherche) grant EPILAND with EuroBiomed label, and P. S., N. Burnashev and N. Bruneau are supported by INSERM.