A Novel CACNA1A Nonsense Variant [c.4054C>T (p.Arg1352⁎)] Causing Episodic Ataxia Type 2

Abstract

Episodic ataxia is a heterogenous group of uncommon neurological disorders characterised by recurrent episodes of vertigo, dysarthria, and ataxia for which a variety of different genetic variations have been implicated. Episodic ataxia type two (EA2) is the most common and also has the largest number of identified causative genetic variants. Treatment with acetazolamide is effective in improving symptoms, so accurate diagnosis is essential. However, a large proportion of patients with EA2 have negative genetic testing. We present a patient with a typical history of EA2 who had a novel variant in the CACNA1A gene not previously described. Report of such variations is important in learning more about the disease and improving diagnostic yield for the patient.

Calcium Channels Genes and Their Epilepsy Phenotypes

“…They described a young girl with a heterozygous de novo missense variant c. 410A > G (p. E137G) in CACNA1A, which was responsible of this clinical phenothype. 87 Some novel pathogenic mutations have been associated with ataxia type 2: an heterozygous variant in exon 25, c.4054C > T (p. Arg 1352) has been discovered in a patient who had a clinical presentation of ataxia type 2 with associated typical features such as migraine and interictal dysarthria 88 ; another novel pathogenic frameshift mutation in CACNA1A (c.3901delC; p. Leu1301Sefs à 19) emerged in a patient with EA2-typical features 89 ; and a novel frameshift mutation in the CACNA1A (c.1642del, p.H548Tfs à 24), leading to premature protein truncation, was identified in a patient with recurrent episodes of leg weakness, dysarthria, clumsiness of hands, and vertigo during the attacks. [90][91][92][93][94][95]…”