title: A novel KCNA1 mutation associated with global delay and persistent cerebellar dysfunction.
abstract: Episodic Ataxia Type 1 is an autosomal dominant disorder characterized by episodes of ataxia and myokymia. It is associated with mutations in the KCNA1 voltage-gated potassium channel gene. In the present study, we describe a family with novel clinical features including persistent cerebellar dysfunction, cerebellar atrophy, and cognitive delay. All affected family members have myokymia and epilepsy, but only one individual has episodes of vertigo. Additional features include postural abnormalities, episodic stiffness and weakness. A novel KCNA1 mutation (c.1222G>T) which replaces a highly conserved valine with leucine at position 408 (p.Val408Leu) was identified in affected family members, and was found to augment the ability of the channel to inactivate. Together, our data suggests that KCNA1 mutations are associated with a broader clinical phenotype, which may include persistent cerebellar dysfunction and cognitive delay.
authors.affiliation: Department of Pediatric Neurology, British Columbia's Children's Hospital, Vancouver, British Columbia, Canada. mdemos@cw.bc.ca
authors.forename: Michelle K
authors.initials: MK
authors.lastname: Demos
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Macri
authors.forename: Kevin
authors.initials: K
authors.lastname: Farrell
authors.forename: Tanya N
authors.initials: TN
authors.lastname: Nelson
authors.forename: Kristine
authors.initials: K
authors.lastname: Chapman
authors.forename: Eric
authors.initials: E
authors.lastname: Accili
authors.forename: Linlea
authors.initials: L
authors.lastname: Armstrong
mesh_terms: D000328:Adult; D000818:Animals; D016466:CHO Cells; D002526:Cerebellar Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002675:Child, Preschool; D006224:Cricetinae; D003412:Cricetulus; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D051662:Kv1.1 Potassium Channel / Q000235:genetics*; D007930:Leucine / Q000235:genetics; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008564:Membrane Potentials / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D014162:Transfection / Q000379:methods; D014633:Valine / Q000235:genetics
chemical_list: C496946:KCNA1 protein, human; D051662:Kv1.1 Potassium Channel; D007930:Leucine; D014633:Valine