title: Dominant-negative mutation p.Arg324Thr in KCNA1 impairs Kv1.1 channel function in episodic ataxia.
abstract: Episodic ataxia type 1 is a rare autosomal dominant neurological disorder caused by mutations in the KCNA1 gene that encodes the α subunit of voltage-gated potassium channel Kv1.1. The functional consequences of identified mutations on channel function do not fully correlate with the clinical phenotype of patients.
  
  
  
  A clinical and genetic study was performed in a family with 5 patients with episodic ataxia type 1, with concurrent epilepsy in 1 of them. Protein expression, modeling, and electrophysiological analyses were performed to study Kv1.1 function.
  
  
  
  Whole-genome linkage and candidate gene analyses revealed the novel heterozygous mutation p.Arg324Thr in the KCNA1 gene. The encoded mutant Kv1.1 channel displays reduced currents and altered activation and inactivation.
  
  
  
  Taken together, we provide genetic and functional evidence that mutation p.Arg324Thr in the KCNA1 gene is pathogenic and results in episodic ataxia type 1 through a dominant-negative effect. © 2016 International Parkinson and Movement Disorder Society.
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Enriqueta
authors.initials: E
authors.lastname: Tristán-Clavijo
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.|Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla, Sevilla, Spain.
authors.forename: Francisco G
authors.initials: FG
authors.lastname: Scholl
authors.affiliation: Grup de Recerca en Neurologia Infantil, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
authors.forename: Alfons
authors.initials: A
authors.lastname: Macaya
authors.affiliation: Servicio de Pediatría, Neuropediatría, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Iglesias
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Rojas
authors.affiliation: Servicio de Biología Molecular, Hospital Universitario Virgen Macarena, Facultad de Medicina, Sevilla, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Lucas
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.|Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla, Sevilla, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Castellano
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Amalia
authors.initials: A
authors.lastname: Martinez-Mir
mesh_terms: D001259:Ataxia / Q000235:genetics* / Q000503:physiopathology*; D004827:Epilepsy / Q000235:genetics / Q000503:physiopathology; D005260:Female; D006801:Humans; D051662:Kv1.1 Potassium Channel / Q000235:genetics*; D008297:Male; D020385:Myokymia / Q000235:genetics* / Q000503:physiopathology*; D010375:Pedigree
chemical_list: C496946:KCNA1 protein, human; D051662:Kv1.1 Potassium Channel
keywords: KCNA1; Kv1.1; electrophysiology; episodic ataxia; mutation