title: Late-onset episodic ataxia type 2 associated with a novel loss-of-function mutation in the CACNA1A gene.
abstract: We report a patient with typical features of episodic ataxia type 2 (EA2) but with onset in the sixth decade and associated interictal hand dystonia. He was found to bear the novel heterozygous missense mutation p.Gly638Asp (c.1913G>A) in the CACNA1A gene. Functional analysis of the mutation on P/Q channels expressed in HEK 293 cells revealed a reduction of Ca(2+) current densities, a left-shift in the apparent reversal potential, the slowing of inactivation kinetics and the increase in the rate of current recovery from inactivation. These results are consistent with a decrease in Ca(2+) permeability through mutant P/Q channels. To our knowledge, this is just the second patient with late onset EA2 linked to a CACNA1A mutation and the first to carry a loss-of-function missense mutation.
authors.affiliation: Grup de Recerca en Neurologia Infantil i Psiquiatria Genètica, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
authors.forename: Ester
authors.initials: E
authors.lastname: Cuenca-León
authors.forename: Isabel
authors.initials: I
authors.lastname: Banchs
authors.forename: Selma A
authors.initials: SA
authors.lastname: Serra
authors.forename: Pilar
authors.initials: P
authors.lastname: Latorre
authors.forename: Noèlia
authors.initials: N
authors.lastname: Fernàndez-Castillo
authors.forename: Roser
authors.initials: R
authors.lastname: Corominas
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Valverde
authors.forename: Víctor
authors.initials: V
authors.lastname: Volpini
authors.forename: José M
authors.initials: JM
authors.lastname: Fernández-Fernández
authors.forename: Alfons
authors.initials: A
authors.lastname: Macaya
authors.forename: Bru
authors.initials: B
authors.lastname: Cormand
mesh_terms: D017668:Age of Onset; D000595:Amino Acid Sequence; D001259:Ataxia / Q000150:complications / Q000235:genetics*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D004421:Dystonia / Q000150:complications / Q000235:genetics; D006801:Humans; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D018408:Patch-Clamp Techniques; D020864:Calcium Channels, N-Type
chemical_list: D002118:Calcium; D015220:Calcium Channels; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type