Mao X - Bruneau N - Gao Q - Becq H - Jia Z - Xi H - Shu L - Wang H - Szepetowski P - Aniksztejn L


Frontiers in cellular neuroscience


The epilepsy of infancy with migrating focal seizures (EIMFS; previously called Malignant migrating partial seizures of infancy) are early-onset epileptic encephalopathies (EOEE) that associate multifocal ictal discharges and profound psychomotor retardation. EIMFS have a genetic origin and are mostly caused by mutations in the gene, and much more rarely in the gene. and respectively encode the K1.1 (Slack) and K1.2 (Slick) subunits of the sodium-dependent voltage-gated potassium channel K. Functional analyses of the corresponding mutant homomeric channels suggested gain-of-function effects. Here, we report two novel, truncating mutations of : one mutation is frameshift (p.L48Qfs43), is situated in the N-terminal domain, and was found in a patient with EOEE (possibly EIMFS); the other mutation is nonsense (p.K564*), is located in the C-terminal region, and was found in a typical EIMFS patient. Using whole-cell patch-clamp recordings, we have analyzed the functional consequences of those two novel mutations on reconstituted K1.2 homomeric and K1.1/K1.2 heteromeric channels in transfected chinese hamster ovary (CHO) cells. We report that both mutations significantly impacted on K function; notably, they decreased the global current density of heteromeric channels by ~25% (p.K564*) and ~55% (p.L48Qfs43). Overall our data emphasize the involvement of in EOEE and provide novel insights into the role of heteromeric K channel in the severe -related epileptic phenotypes. This may have important implications regarding the elaboration of future treatment.

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