title: A novel mutation in KCNA1 causes episodic ataxia without myokymia.
abstract: We describe a unique family in which several individual are affected with episodes of ataxia that best fit the phenotype of episodic ataxia type 2 (EA2). All of the affected family members had episodes typically lasting for several hours, and none of them had muscle abnormalities including myokymia. Episodic ataxia type 1 (EA1) was not considered initially as a clinical diagnosis for the affected individuals in this family. However, by linkage mapping, sequencing and polymorphism analysis, all affecteds were found to have a novel mutation in KCNA1. Numerous missense mutations have been described previously in KCNA1 that cause EA1. The mutation c.1025G>T replaces a highly conserved serine with isoleucine at position 342 (p.Ser342Ile) in the highly conserved fifth transmembrane domain of the KCNA1. This mutation leads to a distinct clinical phenotype without myokymia broadening the scope of clinical characteristics of EA1 and highlighting the heterogeneity of phenotypic effects from distinct missense mutations.
authors.affiliation: Department of Human Genetics, University of California, Los Angeles, California, USA.
authors.forename: Hane
authors.initials: H
authors.lastname: Lee
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Joanna C
authors.initials: JC
authors.lastname: Jen
authors.forename: Chiara
authors.initials: C
authors.lastname: Sabatti
authors.forename: Robert W
authors.initials: RW
authors.lastname: Baloh
authors.forename: Stanley F
authors.initials: SF
authors.lastname: Nelson
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001259:Ataxia / Q000235:genetics* / Q000503:physiopathology; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D051662:Kv1.1 Potassium Channel; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D020385:Myokymia; D010375:Pedigree; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: C496946:KCNA1 protein, human; D024642:Potassium Channels, Voltage-Gated; D051662:Kv1.1 Potassium Channel