variants cause childhood partial epilepsy and infantile spasms with favourable outcomes.

BACKGROUND

The gene plays vital roles in embryonic development, cell proliferation, neuronal differentiation and neuronal death. This study aims to explore the relationship between variants and epilepsy.

METHODS

Whole-exome sequencing was performed in a cohort of 378 patients with partial (focal) epilepsy. A knockdown model was used to validate the association between and epilepsy.

RESULTS

Compound heterozygous variants were identified in eight unrelated cases. The burden of variants was significantly higher in the case cohort, shown by multiple/specific statistical analyses. In knockdown flies, the incidence and duration of seizure-like behaviour were significantly greater than those in the controls. The knockdown flies exhibited more firing in excitatory neurons. All patients presented partial seizures. The five patients with variants in the C-terminus/N-terminus presented mild partial epilepsy. The other three patients included one who experienced frequent non-convulsive status epilepticus and two who had early spasms. These three patients had also neurodevelopmental abnormalities and were diagnosed as developmental epileptic encephalopathy (DEE), but achieved seizure-free after antiepileptic-drug treatment without adrenocorticotropic-hormone/steroids. The analyses of temporal expression (genetic dependent stages) indicated that orthologous were highly expressed in the embryonic stage and decreased dramatically after birth.

CONCLUSION

is a novel causative gene of childhood partial epilepsy and DEE. The patients of infantile spasms achieved seizure-free after treatment without adrenocorticotropic-hormone/steroids implies a significance of genetic diagnosis in precise treatment. The genetic dependent stage provided an insight into the underlying mechanism of the evolutional course of illness.