J Mov Disord.  2021 Jan;14(1):70-74. 10.14802/jmd.20082.

New Nonsense Variant c.2983G>T; p.Glu995* in the CACNA1A Gene Causes Progressive Autosomal Dominant Ataxia

• Saathoff Y
• Biskup S
• Funke C
• Roth C

• KMID: 2511491
• DOI: http://doi.org/10.14802/jmd.20082

Abstract

The genetic testing of hereditary ataxias includes screening for CAG-repeat expansions as well as pathogenic variants and nontranslated oligonucleotide expansion, which can cause spinocerebellar ataxia (SCA). Genotype-phenotype correlations of several SCA subtypes are difficult to establish, and the underlying mechanisms remain unclear. Here, we report a 58-year-old male patient who presented with severe generalized ataxia, horizontal gaze-evoked nystagmus, cognitive impairment and a positive family history of gait difficulties. Genetic panel diagnostics revealed a new nonsense pathogenic variant in the CACNA1A gene (c.2983G>T; p. Glu995*) that segregated with the phenotype in three clinically affected family members. This gene is related to SCA type 6 (SCA6), episodic ataxia type 2, familial hemiplegic migraine type 1, among others. When it is supported by the clinical findings and family history, additional DNA sequencing beyond fragment length analysis should be performed.

Keyword

Channelopathies; Spinocerebellar ataxia type 6