title: Functional analysis of a novel potassium channel (KCNA1) mutation in hereditary myokymia.
abstract: 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.
authors.affiliation: Department of Pharmacology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Haijun
authors.initials: H
authors.lastname: Chen
authors.forename: Christian
authors.initials: C
authors.lastname: von Hehn
authors.forename: Leonard K
authors.initials: LK
authors.lastname: Kaczmarek
authors.forename: Laura R
authors.initials: LR
authors.lastname: Ment
authors.forename: Barbara R
authors.initials: BR
authors.lastname: Pober
authors.forename: Fuki M
authors.initials: FM
authors.lastname: Hisama
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D004576:Electromyography; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D051662:Kv1.1 Potassium Channel / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D020385:Myokymia / Q000235:genetics* / Q000503:physiopathology; D010802:Phylogeny
chemical_list: C496946:KCNA1 protein, human; D051662:Kv1.1 Potassium Channel