Chen Haijun, von Hehn Christian, Kaczmarek Leonard K, Ment Laura R, Pober Barbara R, Hisama Fuki M
Department of Pharmacology, Yale University School of Medicine, New Haven, CT, USA.
Neurogenetics. 2007 Apr;8(2):131-5. doi: 10.1007/s10048-006-0071-z. Epub 2006 Nov 29.
Myokymia is characterized by spontaneous, involuntary muscle fiber group contraction visible as vermiform movement of the overlying skin. Myokymia with episodic ataxia is a rare, autosomal dominant trait caused by mutations in KCNA1, encoding a voltage-gated potassium channel. In the present study, we report a family with four members affected with myokymia. Additional clinical features included motor delay initially diagnosed as cerebral palsy, worsening with febrile illness, persistent extensor plantar reflex, and absence of epilepsy or episodic ataxia. Mutation analysis revealed a novel c.676C>A substitution in the potassium channel gene KCNA1, resulting in a T226K nonconservative missense mutation in the Kv1.1 subunit in all affected individuals. Electrophysiological studies of the mutant channel expressed in Xenopus oocytes indicated a loss of function. Co-expression of WT and mutant cRNAs significantly reduced whole-oocyte current compared to expression of WT Kv1.1 alone.
肌束震颤的特征是自发、非自主的肌纤维群收缩，表现为覆盖其上的皮肤出现蠕虫样运动。伴有发作性共济失调的肌束震颤是一种罕见的常染色体显性性状，由编码电压门控钾通道的KCNA1基因突变引起。在本研究中，我们报告了一个有四名成员患肌束震颤的家族。其他临床特征包括最初被诊断为脑瘫的运动发育迟缓、发热性疾病时病情加重、持续的伸跖反射，以及无癫痫或发作性共济失调。突变分析显示钾通道基因KCNA1中存在一个新的c.676C>A替换，导致所有受影响个体的Kv1.1亚基中出现T226K非保守错义突变。对非洲爪蟾卵母细胞中表达的突变通道进行电生理研究表明其功能丧失。与单独表达野生型Kv1.1相比，野生型和突变型cRNA的共表达显著降低了全卵母细胞电流。
