Hallmann K, Durner M, Sander T, Steinlein O K
Institute for Human Genetics, Rheinische Friedrich-Wilhelms-University of Bonn, Germany.
Am J Med Genet. 2000 Feb 7;96(1):8-11. doi: 10.1002/(sici)1096-8628(20000207)96:1<8::aid-ajmg3>3.0.co;2-s.
Genetic factors play a major role in the etiology of idiopathic generalized epilepsy. However, in most syndromes, especially the common ones, multiple genetic factors seem to be involved. Mutations in K(+) channel genes have previously found to be associated with epilepsy both in humans and in mice. The weaver mice phenotype, characterized by ataxia, tremor, male infertility, and tonic-clonic seizures, is caused by a point mutation in the inwardly rectifier K(+) channel gene KCNJ6 (GIRK2). A knockout mouse model deprived of functional KCNJ6 protein is susceptible to spontaneous and provoked seizures without showing the histological signs of neuronal cell death found in the weaver mouse. Thus, the KCNJ6 gene seems to play an important role in seizure control. We therefore performed a mutation analysis of KCNJ6 and the related KCNJ3 gene in 38 patients with juvenile myoclonic epilepsy (JME). Two novel same-sense nucleotide exchanges were identified, but none of these changed the coding sequence. These results do not support a major role for the KCNJ6/KCNJ3 heteromeric receptor in the etiology of JME. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:8-11, 2000
遗传因素在特发性全身性癫痫的病因中起主要作用。然而，在大多数综合征中，尤其是常见的综合征，似乎涉及多种遗传因素。先前已发现钾离子通道基因突变在人类和小鼠中均与癫痫有关。织工小鼠的表型特征为共济失调、震颤、雄性不育和强直阵挛性发作，是由内向整流钾离子通道基因KCNJ6（GIRK2）中的一个点突变引起的。缺乏功能性KCNJ6蛋白的基因敲除小鼠模型易发生自发性和诱发性癫痫发作，但未表现出织工小鼠中发现的神经元细胞死亡的组织学迹象。因此，KCNJ6基因似乎在癫痫控制中起重要作用。因此，我们对38例青少年肌阵挛性癫痫（JME）患者进行了KCNJ6和相关KCNJ3基因的突变分析。鉴定出两个新的同义核苷酸交换，但这些均未改变编码序列。这些结果不支持KCNJ6/KCNJ3异聚体受体在JME病因中起主要作用。《美国医学遗传学杂志》（神经精神遗传学）96:8 - 11，2000
