Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A.
Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A.
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SCN1A周围常见的遗传变异相关的癫痫，海马硬化和发热性癫痫发作。
DOI：
10.1093/brain/awt233
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发表时间：
2013-10
期刊：
影响因子：
--
通讯作者：
Sisodiya SM
中科院分区：
文献类型：
--
作者：
Kasperaviciute D;Catarino CB;Matarin M;Leu C;Novy J;Tostevin A;Leal B;Hessel EV;Hallmann K;Hildebrand MS;Dahl HH;Ryten M;Trabzuni D;Ramasamy A;Alhusaini S;Doherty CP;Dorn T;Hansen J;Krämer G;Steinhoff BJ;Zumsteg D;Duncan S;Kälviäinen RK;Eriksson KJ;Kantanen AM;Pandolfo M;Gruber-Sedlmayr U;Schlachter K;Reinthaler EM;Stogmann E;Zimprich F;Théâtre E;Smith C;O'Brien TJ;Meng Tan K;Petrovski S;Robbiano A;Paravidino R;Zara F;Striano P;Sperling MR;Buono RJ;Hakonarson H;Chaves J;Costa PP;Silva BM;da Silva AM;de Graan PN;Koeleman BP;Becker A;Schoch S;von Lehe M;Reif PS;Rosenow F;Becker F;Weber Y;Lerche H;Rössler K;Buchfelder M;Hamer HM;Kobow K;Coras R;Blumcke I;Scheffer IE;Berkovic SF;Weale ME;UK Brain Expression Consortium;Delanty N;Depondt C;Cavalleri GL;Kunz WS;Sisodiya SM
癫痫包括几种综合征，其中最常见的是内侧颞叶癫痫伴海马硬化。内侧颞叶癫痫伴海马硬化的癫痫发作通常具有耐药性，内侧颞叶癫痫伴海马硬化通常与重要的合并症相关，因此需要寻求更好的理解和治疗。内侧颞叶癫痫伴海马硬化的原因尚不清楚，但与儿童热性惊厥有关。几种罕见的以热性惊厥为特征的癫痫是由SCN 1A突变引起的，SCN 1A编码许多抗癫痫药物靶向的脑表达钠通道亚基。我们在1018名内侧颞叶癫痫伴海马硬化患者和7552名对照受试者中进行了全基因组关联研究，并在包括959名内侧颞叶癫痫伴海马硬化患者和3591名对照受试者的独立样本集中进行了验证。为了分析与热性惊厥病史相关的变异，我们测试了伴有海马硬化的内侧颞叶癫痫病例（总体n = 757）和无热性惊厥病史的病例（总体n = 803）。荟萃分析显示，在染色体2q24.3上的钠通道基因簇[rs7587026，在SCN 1A基因的内含子内，P = 3.36 × 10−9，比值比（A）= 1.42，95%置信区间：1.26-1.59]，内侧颞叶癫痫与海马硬化伴热性惊厥在全基因组范围内显著相关。在172例热性惊厥患者中，他们在13岁的前瞻性随访中没有发生癫痫，6456例对照组中，没有发现rs7587026与热性惊厥的相关性。这些研究结果表明，SCN 1A参与一个共同的癫痫综合征，提供新的方向，生物学的了解内侧颞叶癫痫与海马硬化症与热性惊厥，并开辟途径，调查预后因素和可能的预防癫痫在一些儿童热性惊厥。
Epilepsy comprises several syndromes, amongst the most common being mesial temporal lobe epilepsy with hippocampal sclerosis. Seizures in mesial temporal lobe epilepsy with hippocampal sclerosis are typically drug-resistant, and mesial temporal lobe epilepsy with hippocampal sclerosis is frequently associated with important co-morbidities, mandating the search for better understanding and treatment. The cause of mesial temporal lobe epilepsy with hippocampal sclerosis is unknown, but there is an association with childhood febrile seizures. Several rarer epilepsies featuring febrile seizures are caused by mutations in SCN1A, which encodes a brain-expressed sodium channel subunit targeted by many anti-epileptic drugs. We undertook a genome-wide association study in 1018 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 7552 control subjects, with validation in an independent sample set comprising 959 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 3591 control subjects. To dissect out variants related to a history of febrile seizures, we tested cases with mesial temporal lobe epilepsy with hippocampal sclerosis with (overall n = 757) and without (overall n = 803) a history of febrile seizures. Meta-analysis revealed a genome-wide significant association for mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures at the sodium channel gene cluster on chromosome 2q24.3 [rs7587026, within an intron of the SCN1A gene, P = 3.36 × 10−9, odds ratio (A) = 1.42, 95% confidence interval: 1.26–1.59]. In a cohort of 172 individuals with febrile seizures, who did not develop epilepsy during prospective follow-up to age 13 years, and 6456 controls, no association was found for rs7587026 and febrile seizures. These findings suggest SCN1A involvement in a common epilepsy syndrome, give new direction to biological understanding of mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures, and open avenues for investigation of prognostic factors and possible prevention of epilepsy in some children with febrile seizures.
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DOI：
10.1038/nrg2544
发表时间：
2009-05
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
Ioannidis JP;Thomas G;Daly MJ
通讯作者：
Daly MJ
影响因子：
4.4
作者：
Martin, Melinda S.;Tang, Bin;Escayg, Andrew
通讯作者：
Escayg, Andrew
影响因子：
4.8
作者：
Cendes, F
通讯作者：
Cendes, F
影响因子：
5.6
作者：
Pittau, Francesca;Bisulli, Francesca;Tinuper, Paolo
通讯作者：
Tinuper, Paolo
影响因子：
3
作者：
Mägi R;Morris AP
通讯作者：
Morris AP