GRIN2A mutations cause epilepsy-aphasia spectrum disorders.
GRIN2A mutations cause epilepsy-aphasia spectrum disorders.
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DOI：
10.1038/ng.2727
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发表时间：
2013-09
期刊：
影响因子：
30.8
通讯作者：
Mefford, Heather C.
中科院分区：
文献类型：
--
作者：
Carvill, Gemma L.;Regan, Brigid M.;Yendle, Simone C.;O'Roak, Brian J.;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.
癫痫-失语综合征（EAS）是一组罕见的、病因不明的严重癫痫性脑病，具有特征性脑电图（EEG）模式和发育退化，特别是影响语言。包括GRIN 2A在内的罕见致病性缺失与神经发育障碍有关。我们试图描述GRIN 2A在519例具有不同癫痫综合征的癫痫性脑病先证者中的致病作用。我们确定了四个先证者与GRIN 2A变异，分离与障碍，在他们的家庭。值得注意的是，所有四个家庭都有EAS，占癫痫失语症病例的9%。我们没有在其他癫痫性脑病（n= 475）和良性儿童癫痫伴中央颞区棘波（n= 81）的先证者中检测到GRIN 2A的致病性变异。据我们所知，我们报告了EAS.GRIN2A突变的第一个单基因原因，仅限于这组病例，这对诊断检测和治疗具有重要意义，并为这组衰弱性疾病的发病机制提供了新的见解。
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 includeGRIN2Ahave been implicated in neurodevelopmental disorders. We sought to delineate the pathogenic role ofGRIN2Ain 519 probands with epileptic encephalopathies with diverse epilepsy syndromes. We identified four probands withGRIN2Avariants 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 inGRIN2Ain 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.GRIN2Amutations 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.
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DOI：
10.1523/jneurosci.5382-09.2010
发表时间：
2010-09-01
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Talukder I;Borker P;Wollmuth LP
通讯作者：
Wollmuth LP
影响因子：
5.6
作者：
Tsai, Meng-Han;Vears, Danya F.;Scheffer, Ingrid E.
通讯作者：
Scheffer, Ingrid E.
影响因子：
5.6
作者：
Berg, Anne T.;Berkovic, Samuel F.;Scheffer, Ingrid E.
通讯作者：
Scheffer, Ingrid E.
影响因子：
11.2
作者：
SCHEFFER, IE;JONES, L;BERKOVIC, SF
通讯作者：
BERKOVIC, SF
影响因子：
30.8
作者：
Carvill, Gemma L.;Heavin, Sinead B.;Yendle, Simone C.;McMahon, Jacinta M.;O'Roak, Brian J.;Cook, Joseph;Khan, Adiba;Dorschner, Michael O.;Weaver, Molly;Calvert, Sophie;Malone, Stephen;Wallace, Geoffrey;Stanley, Thorsten;Bye, Ann M. E.;Bleasel, Andrew;Howell, Katherine B.;Kivity, Sara;Mackay, Mark T.;Rodriguez-Casero, Victoria;Webster, Richard;Korczyn, Amos;Afawi, Zaid;Zelnick, Nathanel;Lerman-Sagie, Tally;Lev, Dorit;Moller, Rikke S.;Gill, Deepak;Andrade, Danielle M.;Freeman, Jeremy L.;Sadleir, Lynette G.;Shendure, Jay;Berkovic, Samuel F.;Scheffer, Ingrid E.;Mefford, Heather C.
通讯作者：
Mefford, Heather C.