Figure 1: NaV1.1 architecture and the location of the patient’s mutation. NaV1.1 consists of one main pore-forming α-subunit and two auxiliary β-subunits. The α-subunit comprises four homologous domains (D1–D4), each with six transmembrane regions (S1–S6). The channel pore is formed by the assembly of four linker regions between the S5 and S6 segments (solid arrowheads). Voltage sensitivity is mediated by positively charged residues in the S4 regions (open arrowheads) that move outward when depolarized to open the channel. The nonsense mutation of the patient was located in D4/S4 (white star), which terminated at the R1645 residue, and the NaV1.1 protein looses the faded protein of the portion.