Figure 6.
Topological location of identified mutations. A, Schematic diagram of α-subunits of the cardiac Na channel (Nav1.5, SCN5A). It consists of 4 domains (DI–DIV), each containing 6 transmembrane-spanning segments. Q646R(fx + X5) is a frame-shift mutation resulting in early truncation of the channel protein in the linker between domains I and II. It is associated with both Brugada syndrome (BrS) and ERS phenotypes. Q270K and D356N are 2 missense mutations located in the region of the pore. B, Diagrammatic representation of the topology of the calcium channel β2b subunit. The SH3–HOOK–GK motif interacts with the voltage-activated Ca2+ channel. K170N, L399F, and D538E are 3 missense mutations identified in infants displaying a BrS phenotype. C, Topology of the β-subunit, KCNE1, of the cardiac slowly activating delayed rectifier channel (IKs). The purple cylinder denotes the transmembrane segment of KCNE1. D76N is a missense mutation identified in patient 5, previously reported as being associated with LQT5 and JLNS2. ERS indicates early repolarization syndrome; FS, frameshift mutation; Non, nonsense mutation. * and #Compound mutations found in the same patient.