Sander T, Janz D, Ramel C, Ross C A, Paschen W, Hildmann T, Wienker T F, Bianchi A, Bauer G, Sailer U
Department of Psychiatry, University Hospital Rudolf Virchow, Berlin, Germany.
Neurology. 1995 Sep;45(9):1713-20. doi: 10.1212/wnl.45.9.1713.
Hereditary factors play a major role in the etiology of idiopathic generalized epilepsies (IGEs). The pivotal function of glutamate receptors (GluRs) in excitatory neurotransmission implicates their involvement in epileptogenesis and genetic susceptibility to IGEs. A trinucleotide repeat polymorphism detected in the 3' untranslated region of the kainate-selective GluR6 receptor gene (GRIK2) on chromosome 6 makes it possible to perform linkage and association studies with this high-ranking candidate gene. The present study tested the hypothesis that allelic variants of GRIK2 contribute to the genetic susceptibility to the common IGEs. Linkage and association analyses were conducted in 63 families ascertained through IGE patients with juvenile myoclonic epilepsy, juvenile absence epilepsy, or childhood absence epilepsy. Our linkage and association results suggest that allelic variants of GRIK2 are not involved in the expression of the common familial IGEs, and radiation hybrid mapping assigns GRIK2 to the chromosomal region 6q16.3-q21. This localization excludes GRIK2 as a candidate for the putative IGE susceptibility locus "EJM1" on the short arm of chromosome 6.
遗传因素在特发性全身性癫痫（IGEs）的病因中起主要作用。谷氨酸受体（GluRs）在兴奋性神经传递中的关键作用表明它们参与癫痫发生以及对IGEs的遗传易感性。在6号染色体上的红藻氨酸选择性GluR6受体基因（GRIK2）的3'非翻译区检测到的三核苷酸重复多态性，使得对这个重要候选基因进行连锁和关联研究成为可能。本研究检验了GRIK2等位基因变异导致常见IGEs遗传易感性的假说。对通过患有青少年肌阵挛性癫痫、青少年失神癫痫或儿童失神癫痫的IGE患者确定的63个家系进行了连锁和关联分析。我们的连锁和关联结果表明，GRIK2等位基因变异不参与常见家族性IGEs的表达，辐射杂种图谱将GRIK2定位到染色体区域6q16.3 - q21。这一定位排除了GRIK2作为6号染色体短臂上假定的IGE易感位点“EJM1”的候选基因。
