Petrovicova Andrea, Brozman Miroslav, Kurca Egon, Gobo Tibor, Dluha Jana, Kalmarova Klaudia, Nosal Vladimir, Hikkelova Martina, Krajciova Adriana, Burjanivova Tatiana, Sivak Stefan
Department of Neurology, Faculty Hospital, Constantine Philosopher University, Spitalska 6, 94901 Nitra, Slovak Republic.
Clinic of Neurology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Kollarova 2, 03659 Martin, Slovak Republic.
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2017 Mar;161(1):107-110. doi: 10.5507/bp.2016.066. Epub 2017 Jan 13.
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.
发作性共济失调（EA）是一种罕见的常染色体显性遗传性神经系统疾病，其特征为共济失调反复发作，持续数分钟至数小时。最常见的亚型是2型发作性共济失调（EA2），由19号染色体p13上钙电压门控通道亚基α1A基因（CACNA1A）的致病性变异引起。
我们研究了一个斯洛伐克的三代家族。从外周血中提取家族成员的基因组DNA，并通过聚合酶链反应进行扩增。通过桑格测序筛选CACNA1A变异。
我们鉴定出四名有共济失调反复发作的家族成员，并进行了复杂的鉴别诊断。直接测序基因分析显示，CACNA1A存在一种新的杂合变异——c.5264A>G（p.Glu1755Gly）位于钙通道α-1A亚基结构域IV的孔环中。
我们在一个有共济失调反复发作症状的斯洛伐克三代家族中鉴定出电压依赖性P/Q型钙通道α-1A亚基的一种新的错义变异体。该杂合错义变异导致结构域IV孔环内一个高度保守的谷氨酸发生改变。
