Gu Wenli, Sander Thomas, Heils Armin, Lenzen Kirsten P, Steinlein Ortrud K
Institute of Human Genetics, University Hospital, Ludwig-Maximillians-University, Goethestr. 29, D-80336 Munich, Germany.
Epilepsy Res. 2005 Aug-Sep;66(1-3):91-8. doi: 10.1016/j.eplepsyres.2005.07.003.
Genetic factors play a major role in the etiology of idiopathic generalized epilepsies (IGE). An oligogenic or polygenic predisposition is suspected in the majority of families with common IGE syndromes. It has been hypothesized that some IGE genes might increase the general level of neuronal excitability while others specify the age of onset and the seizure type. The EFHC1 gene on 6p12-p11 was previously described as the first susceptibility gene for juvenile myoclonic epilepsy (JME). EFHC1 codes for a protein of unknown function that is characterized by Ca2+-binding EF-hand motifs and DM10 domains. We have now cloned the brain-expressed paralog EFHC2 (Xp11.3) and carried out an association study of six single nucleotide polymorphisms (SNPs) in a large sample of 654 German IGE patients and 662 population controls. A tentative association was found between the amino acid exchange S430Y in exon 9 of EFHC2 and 97 male JME patients (chi2=4.705, d.f.=1, P=0.030; OR=2.17; 95-CI: 1.06-4.43). The allelic association was even stronger for the 81 males with "classical" JME (JME without absence seizures) (chi2=6.06, d.f.=1, P=0.014; OR=2.46; 95-CI: 1.18-5.13). An association with the gonosomal gene EFHC2 would be in accordance with the observed preponderance of maternal inheritance in JME maternal inheritance of JME. Independent replication studies are needed to further analyse the tentative association described here.
遗传因素在特发性全身性癫痫（IGE）的病因中起主要作用。在大多数患有常见IGE综合征的家庭中，怀疑存在寡基因或多基因易感性。据推测，一些IGE基因可能会提高神经元兴奋性的总体水平，而其他基因则决定发病年龄和癫痫发作类型。位于6p12 - p11的EFHC1基因先前被描述为青少年肌阵挛性癫痫（JME）的首个易感基因。EFHC1编码一种功能未知的蛋白质，其特征在于具有Ca2 +结合EF手基序和DM10结构域。我们现已克隆了在大脑中表达的旁系同源基因EFHC2（Xp11.3），并在654名德国IGE患者和662名人群对照的大样本中对六个单核苷酸多态性（SNP）进行了关联研究。在EFHC2外显子9中的氨基酸交换S430Y与97名男性JME患者之间发现了初步关联（卡方值= 4.705，自由度= 1，P = 0.030；比值比= 2.17；95%可信区间：1.06 - 4.43）。对于81名患有“典型”JME（无失神发作的JME）的男性，等位基因关联更强（卡方值= 6.06，自由度= 1，P = 0.014；比值比= 2.46；95%可信区间：1.18 - 5.13）。与性染色体基因EFHC2的关联将与JME中观察到的母系遗传优势一致。需要进行独立的重复研究以进一步分析此处描述的初步关联。
