GRIN2A mutations in acquired epileptic aphasia and related childhood focal epilepsies and encephalopathies with speech and language dysfunction

被引：337

作者：

Lesca, Gaetan ^{[1
,2
,3
,4
]}

Rudolf, Gabrielle ^{[4
,5
,6
]}

Bruneau, Nadine ^{[4
,7
,8
,9
]}

Lozovaya, Natalia ^{[7
,8
,9
,10
]}

Labalme, Audrey ^{[1
,4
]}

Boutry-Kryza, Nadia ^{[3
,4
,11
]}

Salmi, Manal ^{[4
,7
,8
,9
]}

Tsintsadze, Timur ^{[4
,7
,8
,9
]}

Addis, Laura ^{[12
]}

Motte, Jacques ^{[4
,13
]}

Wright, Sukhvir ^{[14
]}

Tsintsadze, Vera ^{[7
,8
,9
]}

Michel, Anne ^{[15
]}

Doummar, Diane ^{[16
]}

Lascelles, Karine ^{[17
]}

Strug, Lisa ^{[18
,19
]}

Waters, Patrick

de Bellescize, Julitta ^{[4
,20
]}

Vrielynck, Pascal ^{[21
]}

de Saint Martin, Anne ^{[4
,22
]}

Ville, Dorothee ^{[4
,23
]}

Ryvlin, Philippe ^{[3
,4
,20
]}

Arzimanoglou, Alexis ^{[3
,4
,20
]}

Hirsch, Edouard ^{[4
,5
,6
]}

Vincent, Angela ^{[14
]}

Pal, Deb ^{[12
]}

Burnashev, Nail ^{[4
,7
,8
,9
]}

Sanlaville, Damien ^{[1
,2
,3
,4
]}

Szepetowski, Pierre ^{[4
,7
,8
,9
]}

机构：

[1] Univ Hosp Lyon, Dept Genet, Lyon, France

[2] Univ Lyon 1, F-69365 Lyon, France

[3] CNRS, INSERM, U1028, UMR 5292,Ctr Rech Neurosci Lyon, Lyon, France

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

[5] Strasbourg Univ Hosp, Dept Neurol, Strasbourg, France

[6] Strasbourg Univ, Strasbourg, France

[7] Aix Marseille Univ, Marseille, France

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

[9] Mediterranean Inst Neurobiol INMED, Marseille, France

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

[11] Univ Hosp Lyon, Med Genet Lab, Lyon, France

[12] Kings Coll London, Inst Psychiat, Dept Clin Neurosci, London, England

[13] Amer Mem Hosp, Dept Pediat A, Reims, France

[14] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Neurosci, Oxford OX3 9DU, England

[15] Univ Hosp Pontchaillou, Dept Neurol, Rennes, France

[16] Armand Trousseau Hosp, Dept Neuropediat, Paris, France

[17] Evelina Childrens Hosp, Dept Paediat Neurol, London, England

[18] Hosp Sick Children, Res Inst, Toronto, ON M5G 1X8, Canada

[19] Univ Toronto, Toronto, ON, Canada

[20] Univ Hosp Lyon, Epilepsy Sleep & Pediat Neurophysiol Dept, Lyon, France

[21] Catholic Univ Louvain, William Lennox Neurol Ctr, Ottignies, Belgium

[22] Strasbourg Univ Hosp, Dept Pediat 1, Strasbourg, France

[23] Univ Hosp Lyon, Dept Neuropediat, Lyon, France

来源：

NATURE GENETICS | 2013年 / 45卷 / 09期

基金：

英国惠康基金;

关键词：

LANDAU-KLEFFNER-SYNDROME; LIGAND-BINDING DOMAIN; SPIKE-AND-WAVES; NMDA RECEPTORS; SLEEP; DISORDERS; DYSKINESIA; CHILDREN; SPECTRUM; LKS;

D O I：

10.1038/ng.2726

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Epileptic encephalopathies are severe brain disorders with the epileptic component contributing to the worsening of cognitive and behavioral manifestations(1). Acquired epileptic aphasia (Landau-Kleffner syndrome, LKS)(2) and continuous spike and waves during slow-wave sleep syndrome (CSWSS)(3) represent rare and closely related childhood focal epileptic encephalopathies of unknown etiology(4,5). They show electroclinical overlap with rolandic epilepsy (the most frequent childhood focal epilepsy) and can be viewed as different clinical expressions of a single pathological entity situated at the crossroads of epileptic, speech, language, cognitive and behavioral disorders(6-10). Here we demonstrate that about 20% of cases of LKS, CSWSS and electroclinically atypical rolandic epilepsy(11-13) often associated with speech impairment can have a genetic origin sustained by de novo or inherited mutations in the GRIN2A gene (encoding the N-methyl-d-aspartate (NMDA) glutamate receptor alpha 2 subunit, GluN2A). The identification of GRIN2A as a major gene for these epileptic encephalopathies provides crucial insights into the underlying pathophysiology.

引用

页码：1061 / +

页数：8

共 36 条

[31] Glutamate Receptor Ion Channels: Structure, Regulation, and Function [J].

Traynelis, Stephen F. ;

Wollmuth, Lonnie P. ;

McBain, Chris J. ;

Menniti, Frank S. ;

Vance, Katie M. ;

Ogden, Kevin K. ;

Hansen, Kasper B. ;

Yuan, Hongjie ;

Myers, Scott J. ;

Dingledine, Ray .

PHARMACOLOGICAL REVIEWS, 2010, 62 (03) :405-496

[32] CSWS-related autistic regression versus autistic regression without CSWS [J].

Tuchman, Roberto .

EPILEPSIA, 2009, 50 :18-20

[33] Landau-Kleffner syndrome: 50 years after [J].

Van Bogaert, Patrick ;

Paquier, Philippe F. .

EPILEPSIA, 2009, 50 :1-2

[34] Exome sequencing identifies GRIN2A as frequently mutated in melanoma [J].

Wei, Xiaomu ;

Walia, Vijay ;

Lin, Jimmy C. ;

Teer, Jamie K. ;

Prickett, Todd D. ;

Gartner, Jared ;

Davis, Sean ;

Stemke-Hale, Katherine ;

Davies, Michael A. ;

Gershenwald, Jeffrey E. ;

Robinson, William ;

Robinson, Steven ;

Rosenberg, Steven A. ;

Samuels, Yardena .

NATURE GENETICS, 2011, 43 (05) :442-+

[35] Single-channel analysis of a point mutation of a conserved serine residue in the S2 ligand-binding domain of the NR2A NMDA receptor subunit [J].

Wyllie, David J. A. ;

Johnston, Alexander R. ;

Lipscombe, Diane ;

Chen, Philip E. .

JOURNAL OF PHYSIOLOGY-LONDON, 2006, 574 (02) :477-489

[36] Control of NMDA Receptor Function by the NR2 Subunit Amino-Terminal Domain [J].

Yuan, Hongjie ;

Hansen, Kasper B. ;

Vance, Katie M. ;

Ogden, Kevin K. ;

Traynelis, Stephen F. .

JOURNAL OF NEUROSCIENCE, 2009, 29 (39) :12045-12058

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