Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.
Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.
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DOI：
10.1038/ng.2646
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发表时间：
2013-07
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.;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.
癫痫性脑病是一组预后不良的毁灭性癫痫，其中大多数病因不明。我们对500名受影响的个体（病例）中的19个已知和46个癫痫脑病候选基因进行靶向大规模平行重测序，以确定涉及的新基因，并调查与已知基因突变相关的表型谱。总体而言，我们在10%的队列中发现了致病突变。46个候选基因中有6个具有1个或多个致病性变体，总共占我们队列的3%。我们发现新发CHD2和SYNGAP1突变是癫痫性脑病的新原因，分别占病例的1.2%和1%。我们还扩展了SCN 1A、SCN 2A和SCN 8A突变解释的表型谱。据我们所知，这是最大的癫痫性脑病病例队列进行靶向再测序。这种快速有效的方法的实施将改变这些疾病的分子病因学的诊断和理解。
Epileptic encephalopathies are a devastating group of epilepsies with poor prognosis, of which the majority are of unknown etiology. We perform targeted massively parallel resequencing of 19 known and 46 candidate genes for epileptic encephalopathy in 500 affected individuals (cases) to identify new genes involved and to investigate the phenotypic spectrum associated with mutations in known genes. Overall, we identified pathogenic mutations in 10% of our cohort. Six of the 46 candidate genes had 1 or more pathogenic variants, collectively accounting for 3% of our cohort. We show thatde novo CHD2andSYNGAP1mutations are new causes of epileptic encephalopathies, accounting for 1.2% and 1% of cases, respectively. We also expand the phenotypic spectra explained bySCN1A,SCN2AandSCN8Amutations. To our knowledge, this is the largest cohort of cases with epileptic encephalopathies to undergo targeted resequencing. Implementation of this rapid and efficient method will change diagnosis and understanding of the molecular etiologies of these disorders.
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DOI：
10.1016/j.mrfmmm.2006.07.012
发表时间：
2007-05-01
影响因子：
2.3
作者：
Marfella, Concetta G. A.;Imbalzano, Anthony N.
通讯作者：
Imbalzano, Anthony N.
影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
Strom, Tim M.
DOI：
10.1073/pnas.1213825109
发表时间：
2012-11-20
影响因子：
11.1
作者：
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通讯作者：
Kingston, Robert E.
影响因子：
30.8
作者：
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通讯作者：
Dibbens, Leanne M.