However, the mechanisms of SCN1A mutations in FHM3 can be complicated: some exhibit loss-of-function effects in heterologous cell systems [109]; a SCN1A T1174S mutation reported in a family with both epileptic and FHM phenotypes can act in both a gain- and loss-of-function manner [105]; and furthermore, the SCN1A L1670 W and L1649Q mutations induce folding and trafficking defects which, when rescued by incubation at lower temperatures, or when expressed in GABAergic cortical neurons, modifies the gating properties leading to an overall gain-of-function [110, 111]. This evidence concerns the gene SCN1A and familial hemiplegic migraine.