title: Brugada Syndrome and PKP2: Evidences and uncertainties.
abstract: Common electrocardiographic patterns in Brugada Syndrome and Arrhythmogenic Cardiomyopathy have been reported despite phenotypic alterations during its clinical course. Recently, potentially pathogenic variants in the PKP2 gene, the most prevalent gene associated with Arrhythmogenic Cardiomyopathy, have been associated with Brugada Syndrome. In addition, in vitro studies demonstrated the interaction between plakophilin-2 and sodium channel, the most prevalent gene associated with Brugada Syndrome. All these facts reinforce the suggested overlapping between both entities but little is known about the pathophysiological mechanisms. We have performed a comprehensive genetic revision of all PKP2 genetic variants currently associated with Brugada Syndrome. In all variants we identified a lack of solid evidences in order to establish a definite genotype-phenotype association. Hence, despite we believe that PKP2 analysis should be considered as a part of molecular genetic testing in Brugada Syndrome patients, comprehensive clinical and molecular studies should be performed before establish pathogenic association. Therefore, PKP2 variants in Brugada Syndrome cases should be interpreted carefully and additional studies including family segregation should be performed before translation into clinical practice.
authors.affiliation: Cardiovascular Genetics Center, IDIBGI - University of Girona, Spain; Medical Sciences Department, School of Medicine, University of Girona, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Campuzano
authors.affiliation: Cardiovascular Genetics Center, IDIBGI - University of Girona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Fernández-Falgueras
authors.affiliation: Cardiovascular Genetics Center, IDIBGI - University of Girona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Iglesias
authors.affiliation: Cardiovascular Genetics Center, IDIBGI - University of Girona, Spain; Medical Sciences Department, School of Medicine, University of Girona, Spain; Familial Cardiomyopathies Unit, Hospital Josep Trueta, Girona, Spain. Electronic address: ramon@brugada.org.
authors.forename: Ramon
authors.initials: R
authors.lastname: Brugada
mesh_terms: D053840:Brugada Syndrome / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D051191:Plakophilins / Q000235:genetics*; D015222:Sodium Channels / Q000235:genetics
chemical_list: C495337:PKP2 protein, human; D051191:Plakophilins; D015222:Sodium Channels
keywords: Brugada Syndrome; Desmosome; PKP2; Sudden cardiac death