title: Novel missense variant of CACNA1A gene in a Slovak family with episodic ataxia type 2.
abstract: BACKGROUND
  Episodic ataxias (EAs) are rare dominantly inherited neurological disorders characterized by recurrent episodes of ataxia lasting minutes to hours. The most common subtype is EA type 2 (EA2) caused by pathogenic variants of calcium voltage-gated channel subunit alpha1 A gene (CACNA1A) on chromosome 19p13.
  
  
  METHODS
  We examined a Slovak three-generation family. Genomic DNA of the family members was extracted from peripheral blood and amplified by polymerase chain reaction. CACNA1A variants were screened by Sanger sequencing.
  
  
  RESULTS
  We identified four family members with recurrent episodes of ataxia. Complex differential diagnosis was performed. Genetic analysis with direct sequencing revealed a novel heterozygous variant of CACNA1A - c.5264A>G (p.Glu1755Gly) located in the pore loop of domain IV of calcium channel alpha-1A subunit.
  
  
  CONCLUSIONS
  We identified a novel missense variant of a voltage-dependent P/Q-type calcium channel alpha-1A subunit in a Slovak three-generation family with recurrent episodes of ataxia. The heterozygous missense variant resulted in changing a highly conserved glutamic acid within the pore loop of domain IV.
authors.affiliation: Department of Neurology, Faculty Hospital, Constantine Philosopher University, Spitalska 6, 94901 Nitra, Slovak Republic.
authors.forename: Andrea
authors.initials: A
authors.lastname: Petrovicova
authors.affiliation: Department of Neurology, Faculty Hospital, Constantine Philosopher University, Spitalska 6, 94901 Nitra, Slovak Republic.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Brozman
authors.affiliation: Clinic of Neurology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Kollarova 2, 03659 Martin, Slovak Republic.
authors.forename: Egon
authors.initials: E
authors.lastname: Kurca
authors.affiliation: Department of Neurology, Faculty Hospital, Constantine Philosopher University, Spitalska 6, 94901 Nitra, Slovak Republic.
authors.forename: Tibor
authors.initials: T
authors.lastname: Gobo
authors.affiliation: Clinic of Neurology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Kollarova 2, 03659 Martin, Slovak Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Dluha
authors.affiliation: Clinic of Neurology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Kollarova 2, 03659 Martin, Slovak Republic.
authors.forename: Klaudia
authors.initials: K
authors.lastname: Kalmarova
authors.affiliation: Clinic of Neurology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Kollarova 2, 03659 Martin, Slovak Republic.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Nosal
authors.affiliation: Alphamedical, s.r.o, Laboratory of Medical Genetics, Radlinskeho 9, 81000 Bratislava.
authors.forename: Martina
authors.initials: M
authors.lastname: Hikkelova
authors.affiliation: Alphamedical, s.r.o, Laboratory of Medical Genetics, Radlinskeho 9, 81000 Bratislava.
authors.forename: Adriana
authors.initials: A
authors.lastname: Krajciova
authors.affiliation: Department of Molecular Biology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Mala Hora 4b, 03659 Martin, Slovak Republic.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Burjanivova
authors.affiliation: Clinic of Neurology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Kollarova 2, 03659 Martin, Slovak Republic.
authors.forename: Stefan
authors.initials: S
authors.lastname: Sivak
mesh_terms: D017668:Age of Onset; D001259:Ataxia / Q000235:genetics*; D015220:Calcium Channels / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D012008:Recurrence; D018154:Slovakia; D055815:Young Adult; D020864:Calcium Channels, N-Type
chemical_list: D015220:Calcium Channels; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type
keywords: CACNA1A; episodic ataxia type 2; novel variant; pore loop