title: Novel splice site CACNA1A mutation causing episodic ataxia type 2.
abstract: Episodic ataxia type 2 (EA-2) is an autosomal dominant neurological disorder, characterized by episodes of ataxia, vertigo, nausea, nystagmus, and fatigue, associated with acetazolamide responsiveness. The disease is caused by mutations in the P/Q-type calcium channel Ca(v)2.1 subunit gene, CACNA1A, located on chromosome 19p13.2. We analyzed a family with 13 affected individuals for linkage to this locus and reached a two-point maximum LOD score of 4.48. A novel CACNA1A mutation, IVS36-2A>G, at the 3' acceptor splice site of intron 36 was identified by sequencing. It is the first described CACNA1A acceptor splice site mutation and the most C-terminal EA-2-causing mutation reported to date.
authors.affiliation: Biomedicum Helsinki, Molecular Medicine Research Program, University of Helsinki, Helsinki, Finland.
authors.forename: M A
authors.initials: MA
authors.lastname: Kaunisto
authors.forename: H
authors.initials: H
authors.lastname: Harno
authors.forename: M
authors.initials: M
authors.lastname: Kallela
authors.forename: H
authors.initials: H
authors.lastname: Somer
authors.forename: R
authors.initials: R
authors.lastname: Sallinen
authors.forename: E
authors.initials: E
authors.lastname: Hämäläinen
authors.forename: P J
authors.initials: PJ
authors.lastname: Miettinen
authors.forename: J
authors.initials: J
authors.lastname: Vesa
authors.forename: A
authors.initials: A
authors.lastname: Orpana
authors.forename: A
authors.initials: A
authors.lastname: Palotie
authors.forename: M
authors.initials: M
authors.lastname: Färkkilä
authors.forename: M
authors.initials: M
authors.lastname: Wessman
mesh_terms: D000293:Adolescent; D000328:Adult; D015220:Calcium Channels / Q000737:chemistry / Q000235:genetics*; D002524:Cerebellar Ataxia / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002888:Chromosomes, Human, Pair 19; D005260:Female; D006801:Humans; D007438:Introns / Q000235:genetics; D008126:Lod Score; D008297:Male; D010375:Pedigree; D010641:Phenotype; D011110:Polymorphism, Genetic; D017434:Protein Structure, Tertiary / Q000235:genetics; D022821:RNA Splice Sites / Q000235:genetics*; D020864:Calcium Channels, N-Type
chemical_list: D015220:Calcium Channels; D022821:RNA Splice Sites; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type