Clinical and molecular data define a diagnosis of arrhythmogenic cardiomyopathy in a carrier of a brugada-syndrome-associated PKP2 mutation

Simone Persampieri, Chiara Assunta Pilato, Elena Sommariva, Angela Serena Maione, Ilaria Stadiotti, Antonio Ranalletta, Margherita Torchio, Antonio Dello Russo, Cristina Basso, Giulio Pompilio, Claudio Tondo, Michela Casella

Research output: Contribution to journalArticlepeer-review

Abstract

Plakophilin-2 (PKP2) is the most frequently mutated desmosomal gene in arrhythmogenic cardiomyopathy (ACM), a disease characterized by structural and electrical alterations predominantly affecting the right ventricular myocardium. Notably, ACM cases without overt structural alterations are frequently reported, mainly in the early phases of the disease. Recently, the PKP2 p.S183N mutation was found in a patient affected by Brugada syndrome (BS), an inherited arrhythmic channelopathy most commonly caused by sodium channel gene mutations. We here describe a case of a patient carrier of the same BS-related PKP2 p.S183N mutation but with a clear diagnosis of ACM. Specifically, we report how clinical and molecular investigations can be integrated for diagnostic purposes, distinguishing between ACM and BS, which are increasingly recognized as syndromes with clinical and genetic overlaps. This observation is fundamentally relevant in redefining the role of genetics in the approach to the arrhythmic patient, progressing beyond the concept of “one mutation, one disease”, and raising concerns about the most appropriate approach to patients affected by structural/electrical cardiomyopathy. The merging of genetics, electroanatomical mapping, and tissue and cell characterization summarized in our patient seems to be the most complete diagnostic algorithm, favoring a reliable diagnosis.

Original languageEnglish
Article number571
JournalGenes
Volume11
Issue number5
DOIs
Publication statusPublished - May 2020

Keywords

  • Arrhythmogenic cardiomyopathy
  • Brugada syndrome
  • Cardiac mesenchymal stromal cells
  • Diagnosis
  • Endomyocardial biopsy
  • Functional studies
  • Mutation
  • PKP2

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Clinical and molecular data define a diagnosis of arrhythmogenic cardiomyopathy in a carrier of a brugada-syndrome-associated PKP2 mutation'. Together they form a unique fingerprint.

Cite this