A potassium channel mutation in neonatal human epilepsy
A potassium channel mutation in neonatal human epilepsy
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DOI：
10.1126/science.279.5349.403
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发表时间：
1998-01-16
期刊：
影响因子：
56.9
通讯作者：
Steinlein, OK
中科院分区：
文献类型：
--
作者：
Biervert, C;Schroeder, BC;Steinlein, OK
良性家族性新生儿惊厥（BFNC）是一种常染色体显性婴儿期癫痫，其基因座定位于人类染色体20q13.3和8q24。通过定位克隆，分离到位于20q13.3上的钾通道基因KCNQ2，发现该基因在脑中表达。KCNQ2在青蛙卵母细胞中的表达导致钾选择电流，该电流随着去极化而缓慢激活。在具有BFNC的大型谱系中，插入5个碱基对将从KCNQ2羧基端删除300多个氨基酸。突变通道的表达不能产生可测量的电流。因此，钾依赖性复极损伤可能导致这种年龄特异性癫痫综合征。
Benign familial neonatal convulsions (BFNC) is an autosomal dominant epilepsy of infancy, with loci mapped to human chromosomes 20q13.3 and 8q24. By positional cloning, a potassium channel gene (KCNQ2) located on 20q13.3 was isolated and found to be expressed in brain. Expression of KCNQ2 in frog (Xenopus laevis) oocytes led to potassium-selective currents that activated slowly with depolarization. In a large pedigree with BFNC, a five-base pair insertion would delete more than 300 amino acids from the KCNQ2 carboxyl terminus. Expression of the mutant channel did not yield measurable currents. Thus, impairment of potassium-dependent repolarization is likely to cause this age-specific epileptic syndrome.