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

• Published in: Journal of movement disorders Vol. 14; no. 1; pp. 70 - 74
• Main Authors: Yannic Saathoff, Saskia Biskup, Claudia Funke, Christian Roth
• Format: Journal Article
• Language: English
• Published: Korean Movement Disorder Society 01.01.2021
• Subjects: channelopathies; spinocerebellar ataxia type 6
• ISSN: 2005-940X; 2093-4939
• DOI: 10.14802/jmd.20082

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.