GRIN2A mutations cause epilepsy-aphasia spectrum disorders

Gemma L. Carvill, Brigid M. Regan, Simone C. Yendle, Brian 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

Research output: Contribution to journalArticle

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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 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
Volume45
Issue number9
DOIs
StatePublished - Sep 2013
Externally publishedYes

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Aphasia
Epilepsy
Brain Diseases
Mutation
Rolandic Epilepsy
Electroencephalography
Language

ASJC Scopus subject areas

  • Genetics

Cite this

Carvill, G. L., Regan, B. M., Yendle, S. C., O'Roak, B., Lozovaya, N., Bruneau, N., ... Mefford, H. C. (2013). GRIN2A mutations cause epilepsy-aphasia spectrum disorders. Nature Genetics, 45(9), 1073-1076. https://doi.org/10.1038/ng.2727

GRIN2A mutations cause epilepsy-aphasia spectrum disorders. / Carvill, Gemma L.; Regan, Brigid M.; Yendle, Simone C.; O'Roak, Brian; Lozovaya, Natalia; Bruneau, Nadine; Burnashev, Nail; Khan, Adiba; Cook, Joseph; Geraghty, Eileen; Sadleir, Lynette G.; Turner, Samantha J.; Tsai, Meng Han; Webster, Richard; Ouvrier, Robert; Damiano, John A.; Berkovic, Samuel F.; Shendure, Jay; Hildebrand, Michael S.; Szepetowski, Pierre; Scheffer, Ingrid E.; Mefford, Heather C.

In: Nature Genetics, Vol. 45, No. 9, 09.2013, p. 1073-1076.

Research output: Contribution to journalArticle

Carvill, GL, Regan, BM, Yendle, SC, O'Roak, B, Lozovaya, N, Bruneau, N, Burnashev, N, Khan, A, Cook, J, Geraghty, E, Sadleir, LG, Turner, SJ, Tsai, MH, Webster, R, Ouvrier, R, Damiano, JA, Berkovic, SF, Shendure, J, Hildebrand, MS, Szepetowski, P, Scheffer, IE & Mefford, HC 2013, 'GRIN2A mutations cause epilepsy-aphasia spectrum disorders', Nature Genetics, vol. 45, no. 9, pp. 1073-1076. https://doi.org/10.1038/ng.2727
Carvill GL, Regan BM, Yendle SC, O'Roak B, Lozovaya N, Bruneau N et al. GRIN2A mutations cause epilepsy-aphasia spectrum disorders. Nature Genetics. 2013 Sep;45(9):1073-1076. https://doi.org/10.1038/ng.2727
Carvill, Gemma L. ; Regan, Brigid M. ; Yendle, Simone C. ; O'Roak, Brian ; Lozovaya, Natalia ; Bruneau, Nadine ; Burnashev, Nail ; Khan, Adiba ; Cook, Joseph ; Geraghty, Eileen ; Sadleir, Lynette G. ; Turner, Samantha J. ; Tsai, Meng Han ; Webster, Richard ; Ouvrier, Robert ; Damiano, John A. ; Berkovic, Samuel F. ; Shendure, Jay ; Hildebrand, Michael S. ; Szepetowski, Pierre ; Scheffer, Ingrid E. ; Mefford, Heather C. / GRIN2A mutations cause epilepsy-aphasia spectrum disorders. In: Nature Genetics. 2013 ; Vol. 45, No. 9. pp. 1073-1076.
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