GRIN2A mutations cause epilepsy-aphasia spectrum disorders

被引：297

作者：

Carvill, Gemma L. ^{[1
]}

Regan, Brigid M. ^{[2
]}

Yendle, Simone C. ^{[2
]}

O'Roak, Brian J. ^{[3
]}

Lozovaya, Natalia ^{[4
,5
,6
,7
]}

Bruneau, Nadine ^{[4
,5
,6
,8
]}

Burnashev, Nail ^{[4
,5
,6
,8
]}

Khan, Adiba ^{[1
]}

Cook, Joseph ^{[1
]}

Geraghty, Eileen ^{[1
]}

Sadleir, Lynette G. ^{[9
]}

Turner, Samantha J. ^{[2
,10
]}

Tsai, Meng-Han ^{[2
]}

Webster, Richard ^{[11
]}

Ouvrier, Robert ^{[11
]}

Damiano, John A. ^{[2
]}

Berkovic, Samuel F. ^{[2
]}

Shendure, Jay ^{[3
]}

Hildebrand, Michael S. ^{[2
]}

Szepetowski, Pierre ^{[4
,5
,6
,8
]}

Scheffer, Ingrid E. ^{[2
,10
,12
]}

Mefford, Heather C. ^{[1
]}

机构：

[1] Univ Washington, Dept Pediat, Div Med Genet, Seattle, WA 98195 USA

[2] Univ Melbourne, Dept Med, Epilepsy Res Ctr, Austin Hlth, Melbourne, Vic, Australia

[3] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA

[4] Mediterranean Inst Neurobiol INMED, Marseille, France

[5] INSERM, UMRS 901, F-13258 Marseille, France

[6] Aix Marseille Univ, Marseille, France

[7] Paris Descartes Univ, INSERM, UMRS 663, Paris, France

[8] French EPILAND Network Epilepsy Language & Dev, Marseille, France

[9] Univ Otago, Sch Med & Hlth Sci, Dept Pediat, Wellington, New Zealand

[10] Univ Melbourne, Dept Pediat, Royal Childrens Hosp, Melbourne, Vic, Australia

[11] Childrens Hosp Westmead, TY Nelson Dept Neurol & Neurosurg, Sydney, NSW, Australia

[12] Florey Inst, Melbourne, Vic, Australia

来源：

NATURE GENETICS | 2013年 / 45卷 / 09期

基金：

英国医学研究理事会; 美国国家卫生研究院;

关键词：

ROLANDIC EPILEPSY; SPEECH; ENCEPHALOPATHIES; CHILDHOOD; SLEEP;

D O I：

10.1038/ng.2727

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 epilepsyaphasia 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.

引用

页码：1073 / +

页数：5

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