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In a single-cohort study, hemizygous missense variants in CCDC22 were identified by trio-based whole-exome sequencing in three unrelated male probands presenting with focal epilepsy of varying severity, including one case with refractory seizures and focal cortical dysplasia (PMID:39426154). All variants were absent from control databases and predicted damaging by multiple in silico tools; protein modelling indicated altered hydrogen bonds and reduced stability, particularly for the variant in the coiled-coil domain correlating with the most severe phenotype. Spatiotemporal expression profiling showed CCDC22 peaks in fetal, infancy, and early adult brain regions, consistent with a developmental role in epileptogenesis. Taken together, the limited number of probands without extended familial segregation and data from a single study support a preliminary association between CCDC22 and epilepsy.
Gene–Disease AssociationLimitedThree unrelated hemizygous cases, no extended segregation, single-cohort study ([PMID:39426154]) Genetic EvidenceLimitedHemizygous missense variants identified in three unrelated male probands; lack of segregation and replication Functional EvidenceLimitedIn silico protein modelling and brain expression studies support impact on NF-κB pathway |