Andrea Petrovicova1, Miroslav Brozman1, Egon Kurca2, Tibor Gobo1, Jana Dluha2, Klaudia Kalmarova2, Vladimir Nosal2, Martina Hikkelova3, Adriana Krajciova3, Tatiana Burjanivova4, Stefan Sivak2. 1. Department of Neurology, Faculty Hospital, Constantine Philosopher University, Spitalska 6, 94901 Nitra, Slovak Republic. 2. Clinic of Neurology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Kollarova 2, 03659 Martin, Slovak Republic. 3. Alphamedical, s.r.o, Laboratory of Medical Genetics, Radlinskeho 9, 81000 Bratislava. 4. Department of Molecular Biology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Mala Hora 4b, 03659 Martin, Slovak Republic.
Abstract
INTRODUCTION: 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. SUBJECTS AND 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. CONCLUSION: 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.
INTRODUCTION: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. SUBJECTS AND 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. CONCLUSION: 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.
Entities:
Keywords:
CACNA1A; episodic ataxia type 2; novel variant; pore loop
Authors: James O Meyer; Shehrazade Dahimene; Karen M Page; Laurent Ferron; Ivan Kadurin; Joseph I J Ellaway; Pengxiang Zhao; Tarun Patel; Simon W Rothwell; Peipeng Lin; Wendy S Pratt; Annette C Dolphin Journal: Cell Rep Date: 2019-10-01 Impact factor: 9.423