Novel missense variant of CACNA1A gene in a Slovak family with episodic ataxia type 2

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. 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. 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. 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.