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ePoster
HUMAN NEURONAL NETWORKS ON MICRO-ELECTRODE ARRAYS AS A TOOL TO ASSESS GENOTYPE-PHENOTYPE CORRELATION IN <EM>CACNA1A</EM>-RELATED DISORDERS
Marina Hommersomand 9 co-authors
Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour
FENS Forum 2026 (2026)
Barcelona, Spain
Board PS05-09AM-379
Presentation
Date TBA
Board: PS05-09AM-379
Event Information
Poster Board
PS05-09AM-379
Poster
View posterAbstract
CACNA1A-related disorders constitute a diverse group of neurological conditions, including ataxia, migraine, and epilepsy. Despite extensive genetic studies, clear genotype-phenotype correlations remain elusive. Moreover, next generation sequencing has identified many variants of uncertain significance (VUS). Here, we leveraged patient-derived and CRISPR/Cas9-engineered human neuronal networks to explore relationships between CACNA1A variants and neurophysiological activity. CACNA1A haploinsufficiency induced subtle alterations in glutamatergic network activity, whereas missense variants had a more pronounced effect on overall network function. Network fingerprints were most affected from patients where ataxia co-occurred with migraine or epilepsy. Furthermore, we analysed the impact of CRISPR/Cas9-induced VUS on network developmental trajectories. Although functional changes could not be directly linked to clinical phenotypes, all tested variants induced measurable alterations in neuronal network function, supporting their classification as likely pathogenic. These findings highlight the potential of human neuronal networks as a translational model for evaluating CACNA1A variant effects and improving clinical variant interpretation.
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