PKP2 mutations associate with Brugada syndrome and with reduced sodium current. (Top left) Representative ECG showing ST-segment elevation, diagnostic for Brugada Syndrome, in one of the five patients carriers of missense mutations on the PKP-2 gene, and correspondent electropherograms showing the specific aminoacid substitution R635Q. (Bottom left) Sodium current amplitude recorded inHL1 cells silenced for PKP-2 (PKP2-KD) transfected with the mutant (red), anempty vector (blue), or wild-ype PKP-2 (black). (Right) pedigree of the family showing co-segregation between the PKP-2 mutation and the clinical Phenotype. Hx = history; SD=sudden death. Adapted from Cerrone et al21.