Kurahashi H, Wang J-w, Ishii A, Kojima T, Wakai S, Kizawa T, Fujimoto Y, Kikkawa K, Yoshimura K, Inoue T, Yasumoto S, Ogawa A, Kaneko S, Hirose S
Department of Pediatrics, School of Medicine, Fukuoka University, Japan.
Neurology. 2009 Oct 13;73(15):1214-7. doi: 10.1212/WNL.0b013e3181bc0158.
Mutations of the genes encoding subunits of potassium voltage-gated channel, KCNQ2 and KCNQ3, have been identified in patients with benign familial neonatal seizures (BFNS). This study set out to determine the frequency of microchromosomal deletions of KCNQ2 or KCNQ3 associated with BFNS.
The study subjects were patients with BFNS (n = 22). Microdeletions were sought by multiplex ligation-dependent probe amplification and then confirmed by fluorescence in situ hybridization and characterized by array-based comparative genomic hybridization.
Heterozygous multiple exonic deletions of KCNQ2 were identified in 4 of 22 patients with BFNS. Concomitant deletions of adjacent genes, including nicotinic cholinergic receptor alpha4 (CHRNA4), were detected in 2 of the 4 cases. The clinical courses of patients with deletions of both KCNQ2 and CHRNA4 were those of typical BFNS, and none presented with the phenotype of autosomal dominant nocturnal frontal lobe epilepsy, some of which are caused by mutations of CHRNA4.
Our findings indicate that the clinical courses of patients with deletions of both KCNQ2 and CHRNA4 are indistinguishable from those of patients with deletions of KCNQ2 only.
在良性家族性新生儿惊厥（BFNS）患者中已鉴定出编码钾离子电压门控通道亚基的基因KCNQ2和KCNQ3的突变。本研究旨在确定与BFNS相关的KCNQ2或KCNQ3微染色体缺失的频率。
研究对象为BFNS患者（n = 22）。通过多重连接依赖探针扩增寻找微缺失，然后通过荧光原位杂交进行确认，并通过基于阵列的比较基因组杂交进行特征分析。
在22例BFNS患者中的4例中鉴定出KCNQ2的杂合多个外显子缺失。在4例中的2例中检测到包括烟碱型胆碱能受体α4（CHRNA4）在内的相邻基因的伴随缺失。KCNQ2和CHRNA4均缺失的患者的临床病程为典型的BFNS，且均未表现出常染色体显性夜间额叶癫痫的表型，其中一些是由CHRNA4突变引起的。
我们的研究结果表明，KCNQ2和CHRNA4均缺失的患者的临床病程与仅KCNQ2缺失的患者的临床病程无法区分。
