Functional and pharmacological characterization of the SCN2A variant p.C258R with mixed gain and loss of function causing developmental and epileptic encephalopathy type 11

Description

Alina Köppel and colleagues examined a single gene variant in 2026 behind a severe childhood epilepsy and developmental disorder. Changes in the gene disrupt a sodium channel that nerve cells need, and drug choice depends on whether a variant makes the channel overactive or underactive. The team studied a child whose new variant resisted standard treatment. They grew the altered channel in lab cells, measured its electrical behavior, and tested three drugs that had helped the child.

The variant showed a mixed picture. Some measures pointed to weaker channel action, including lower current and faster shutdown under repeated signals. Others pointed to stronger action, such as slower closing in certain tests. Two standard blocking drugs still worked, though one worked less well on the altered channel than on the normal one. The authors argue that blockers with strong use-dependent action may suit such mixed cases best.

Catalog record

Source: https://europepmc.org/articles/PMC13595215