“These results genetically implicated K305T as an autosomal dominant, possibly disease-causing trait,” the authors noted.
ICK variants were also present in 24 of the 310 database patients who had juvenile myoclonic epilepsy (8%). Of these, nine belonged to families with other affected members. The researchers tested 24 ICK variants for pathogenicity and determined that 13 exerted significant juvenile myoclonic epilepsy risk, with odds ratios exceeding 5.0.
When the researchers looked for these variants in the Genome Aggregation Database (gnomAD), they found that 12 of the variants were present but extremely rare, and eight were absent. They also found an additional ICK variant in a Mexican patient who was in gnomAD. That variant was a benign polymorphism in Africans.
Dr. Bailey and her colleagues thus concluded that 21 ICK variants in 22 patients with juvenile myoclonic epilepsy accounted for 7% of the juvenile myoclonic epilepsy among the 310 cases examined.
Experiments in Mice
The team also conducted a series of in vitro and in vivo mouse experiments. They determined that ICK variants impaired the migration of neuronal progenitor cells and lowered their mitotic index. ICK transgenic mice during light sleep displayed muscle movements similar to human myoclonic seizures. These mice also displayed diffuse polyspike brain waves on EEG recordings.