KCNQ2 and KCNQ3 potassium channel genes in benign familial neonatal convulsions:: expansion of the functional and mutation spectrum
KCNQ2 and KCNQ3 potassium channel genes in benign familial neonatal convulsions:: expansion of the functional and mutation spectrum
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DOI：
10.1093/brain/awg286
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发表时间：
2003-12-01
期刊：
影响因子：
14.5
通讯作者：
Leppert, MF
中科院分区：
文献类型：
--
作者：
Singh, NA;Westenskow, P;Leppert, MF
良性家族性新生儿惊厥是一种罕见的常染色体显性遗传的新生儿全身性癫痫。癫痫发作在出生后的最初几天反复发生，并在大约4个月大时缓解。本实验室以前克隆了两个新的钾通道基因KCNQ 2和KCNQ 3，并发现它们在BFNC患者中发生突变。在这份报告中，我们的特点，以前报道的KCNQ 2基因间质缺失的断点，并显示，只有KCNQ 2被删除。我们确定了KCNQ 2中的11个新突变和KCNQ 3钾通道基因中的一个新突变。在一个家庭中，表型扩展到新生儿癫痫发作，包括罗兰癫痫发作，和一个子集的家庭在婴儿期发作。在非洲爪蟾卵母细胞表达系统中，我们表征了五个KCNQ 2和一个KCNQ 3致病突变。这些突变导致可变的功能丧失，并对KCNQ 2/KCNQ 3异源多聚体通道的生物物理特性产生选择性影响。我们在这里报告的第一个显性负突变KCNQ 2，有一个表型的新生儿癫痫发作没有永久性临床中枢神经系统损害。
Benign familial neonatal convulsions (BFNC) is a rare autosomal dominant generalized epilepsy of the newborn infant. Seizures occur repeatedly in the first days of life and remit by approximately 4 months of age. Previously our laboratory cloned two novel potassium channel genes, KCNQ2 and KCNQ3, and showed that they are mutated in patients with BFNC. In this report, we characterize the breakpoints of a previously reported interstitial deletion in the KCNQ2 gene and show that only KCNQ2 is deleted. We identify 11 novel mutations in KCNQ2 and one novel mutation in the KCNQ3 potassium channel genes. In one family, the phenotype extends beyond neonatal seizures and includes rolandic seizures, and a subset of families has onset of seizures in infancy. In the Xenopus oocyte expression system, we characterize five KCNQ2 and one KCNQ3 disease-causing mutations. These mutations cause a variable loss of function, and selective effects on the biophysical properties of KCNQ2/KCNQ3 heteromultimeric channels. We report here the first dominant negative mutation in KCNQ2 that has a phenotype of neonatal seizures without permanent clinical CNS impairment.