Missense Mutations in Plakophilin-2 Cause Sodium Current Deficit and Associate With a Brugada Syndrome Phenotype

Study Questions:

Can plakophilin-2 (PKP2) gene variants cause Brugada syndrome (BrS)?


Genetic analysis looking for PKP2 variants was performed in 200 patients with BrS, no evidence of arrhythmogenic right ventricular cardiomyopathy (ARVC), and no gene mutations known to be associated with BrS.


A missense mutation in PKP2 was identified in five patients. Laboratory testing demonstrated that the mutation was associated with a reduction in sodium current (INa).


The authors concluded that a PKP2 mutation can cause BrS.


Mutations known to cause ARVC are located most often in the PKP2 gene and cause abnormalities in intercellular coupling. This study demonstrates that a mutation in PKP2 also can cause BrS by impairing sodium current.

Clinical Topics: Arrhythmias and Clinical EP, Genetic Arrhythmic Conditions

Keywords: Brugada Syndrome, Mutation, Missense, Sodium, Genetic Testing, Plakophilins

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