Scheffer Ingrid E, Harkin Louise A, Grinton Bronwyn E, Dibbens Leanne M, Turner Samantha J, Zielinski Marta A, Xu Ruwei, Jackson Graeme, Adams Judith, Connellan Mary, Petrou Steven, Wellard R Mark, Briellmann Regula S, Wallace Robyn H, Mulley John C, Berkovic Samuel F
Department of Medicine (Neurology), University of Melbourne, Melbourne, Victoria, Australia.
Brain. 2007 Jan;130(Pt 1):100-9. doi: 10.1093/brain/awl272. Epub 2006 Oct 4.
SCN1B, the gene encoding the sodium channel beta 1 subunit, was the first gene identified for generalized epilepsy with febrile seizures plus (GEFS+). Only three families have been published with SCN1B mutations. Here, we present four new families with SCN1B mutations and characterize the associated phenotypes. Analysis of SCN1B was performed on 402 individuals with various epilepsy syndromes. Four probands with missense mutations were identified. Detailed electroclinical phenotyping was performed on all available affected family members including quantitative MR imaging in those with temporal lobe epilepsy (TLE). Two new families with the original C121W SCN1B mutation were identified; novel mutations R85C and R85H were each found in one family. The following phenotypes occurred in the six families with SCN1B missense mutations: 22 febrile seizures, 20 febrile seizures plus, five TLE, three other GEFS+ phenotypes, two unclassified and ten unaffected individuals. All individuals with confirmed TLE had the C121W mutation; two underwent temporal lobectomy (one with hippocampal sclerosis and one without) and both are seizure free. We confirm the role of SCN1B in GEFS+ and show that the GEFS+ spectrum may include TLE alone. TLE with an SCN1B mutation is not a contraindication to epilepsy surgery.
SCN1B基因编码钠通道β1亚基，是首个被鉴定与热性惊厥附加症（GEFS+）相关的全身性癫痫的基因。仅有三个携带SCN1B突变的家系被报道。在此，我们呈现四个携带SCN1B突变的新家系，并对相关表型进行特征描述。对402例患有各种癫痫综合征的个体进行了SCN1B分析。鉴定出四名携带错义突变的先证者。对所有可获得的受累家庭成员进行了详细的电临床表型分析，包括对颞叶癫痫（TLE）患者进行定量磁共振成像。鉴定出两个携带原始C121W SCN1B突变的新家系；在一个家系中分别发现了新突变R85C和R85H。在六个携带SCN1B错义突变的家系中出现了以下表型：22例热性惊厥、20例热性惊厥附加症、5例TLE、3例其他GEFS+表型、2例未分类以及10例未受累个体。所有确诊为TLE的个体均携带C121W突变；两名患者接受了颞叶切除术（一名伴有海马硬化，一名无海马硬化），两人术后均无癫痫发作。我们证实了SCN1B在GEFS+中的作用，并表明GEFS+谱系可能仅包括TLE。携带SCN1B突变的TLE并非癫痫手术的禁忌证。
