2021/10/14 by Yuliia V. Nikonishyna, Nadine J. Ortner, Teresa Kaserer +7 · 1 citation
Neuroscience · Medicine · Biochemistry, Genetics and Molecular Biology · Chemistry · #Genetic Neurodegenerative Diseases #Amyotrophic Lateral Sclerosis Research #Nuclear Structure and Function #Missense mutation #Spinocerebellar ataxia #Mutant #Mutation #Ataxia #Gating #Mutant protein #Protein subunit #Trinucleotide repeat expansion #Loss function #Genetics #Wild type #Biology #Molecular biology #Chemistry #Phenotype #Biophysics #Allele #Gene #Neuroscience
paper · doi:10.1002/mds.28835
openalex publication_date 2021/10/14 · openalex created_date 2021/10/25 · openalex updated_date 2026/07/29
BACKGROUND: Spinocerebellar ataxia (SCA) is a progressive, autosomal dominant neurodegenerative disorder typically associated with CAG repeat expansions. OBJECTIVE: channel found in a 63-year-old woman with SCA with no CAG repeat expansion. METHODS: We examined the effect of the C256F variant on channel function using whole-cell patch-clamp recordings in transfected tsA-201 cells. RESULTS: current density was significantly reduced in the mutant compared to wild-type, which could not be explained by lower expression levels of mutant Cav2.1 α1- protein. Together with a significant increase in current inactivation, this is consistent with a loss of channel function. Molecular modeling predicted disruption of a conserved disulfide bond through the C256F variant. CONCLUSIONS: Our results support the pathogenicity of the C256F variant for the SCA phenotype and provide further insight into Cav2.1 structure and function.