Summary
In a study focusing on CSNK2A1's role in human disease, whole exome sequencing identified a de novo, likely pathogenic intronic variant in CSNK2A1 in an eight-year-old female presenting with myoclonic and tonic seizures with onset in infancy, along with mild cognitive and language delays. The intronic mutation is predicted to cause abnormal gene splicing, leading to CSNK2A1 haploinsufficiency. Clinical phenotype improvement was noted with seizure response to felbamate and consequently significant cognitive and language development. The mutation is characterized as being de novo with tested inheritance, further supporting the link between the CSNK2A1 variant and the observed phenotype. No functional studies are reported in the dataset, leaving a gap in the direct assessment of the variant's impact on protein function or gene expression.
Evidence of Haploinsufficiency
Patient Identifier: eight-year-old female
Mutation Type: intronic variant
Mutation Details: likely pathogenic, intronic variant in CSNK2A1
Clinical Phenotype: myoclonic and tonic seizures with onset in infancy, mild cognitive and language delays
Inheritance Tested: Yes
Effect on Gene Function: predicted to cause abnormal gene splicing
Direct Quote: "Whole exome sequencing revealed a de novo, likely pathogenic, intronic variant in CSNK2A1. She has myoclonic and tonic seizures with onset in infancy, which responded well to felbamate. She has mild cognitive and language delays, but has caught up significantly since her seizures have improved."
Location in Paper: Epilepsy Research 150 (2019) 70–77
Clinical Features
Feature: myoclonic and tonic seizures with onset in infancy
Frequency: observed in patient within the study
Direct Quote: "She has myoclonic and tonic seizures with onset in infancy..."
Location in Paper: Epilepsy Research 150 (2019) 70–77
Feature: mild cognitive and language delays
Frequency: observed in patient within the study
Direct Quote: "She has mild cognitive and language delays, but has caught up significantly since her seizures have improved."
Location in Paper: Epilepsy Research 150 (2019) 70–77