title: Sca13.
abstract: Spinocerebellar ataxia 13 (SCA13), initially described in a four-generation French family, has now also been characterized in a large Filipino pedigree. Ongoing investigations continue to identify additional SCA13 families and individuals. Recently, studies have shown that mutations in the voltage-gated potassium channel KCNC3 are causative for SCA13. Sequence analysis of KCNC3 revealed mutations 1554G-->A (R420H) in the Filipino and 1639C-->A (F448L) in the French pedigrees. Both mutations alter KCNC3 function in a Xenopus laevis oocyte expression system. KCNC3(R420H), located in the voltage sensor of the channel, has no detectable channel activity when expressed alone, and strong dominant negative effects when coexpressed with wild-type KCNC3. KCNC3(F448L) shifts the activation curve in the negative direction and causes an approximately sevenfold slowing of channel closure. These mutations are expected to change the output characteristics of fast-spiking cerebellar neurons, where KCNC channels confer capacity for high-frequency repetitive firing.
authors.affiliation: Department of Neurology, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL 32610, USA. mwaters@neurology.ufl.edu
authors.forename: M F
authors.initials: MF
authors.lastname: Waters
authors.forename: S M
authors.initials: SM
authors.lastname: Pulst
mesh_terms: D000328:Adult; D017668:Age of Onset; D005260:Female; D016368:Frameshift Mutation; D005602:France; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D010679:Philippines; D051670:Shaw Potassium Channels / Q000235:genetics*; D020754:Spinocerebellar Ataxias / Q000235:genetics*
chemical_list: C489594:KCNC3 protein, human; D009419:Nerve Tissue Proteins; D051670:Shaw Potassium Channels