Diagnostics (Nov 2020)

A Novel <i>DSP</i> Truncating Variant in a Family with Episodic Myocardial Injury in the Course of Arrhythmogenic Cardiomyopathy—A Possible Role of a Low Penetrance <i>NLRP3</i> Variant

  • Przemysław Chmielewski,
  • Grażyna T. Truszkowska,
  • Piotr Kukla,
  • Joanna Zakrzewska-Koperska,
  • Mateusz Śpiewak,
  • Małgorzata Stępień-Wojno,
  • Maria Bilińska,
  • Anna Lutyńska,
  • Rafał Płoski,
  • Zofia T. Bilińska

DOI
https://doi.org/10.3390/diagnostics10110955
Journal volume & issue
Vol. 10, no. 11
p. 955

Abstract

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Mono-allelic dominant mutations in the desmoplakin gene (DSP) have been linked to known cardiac disorders, such as arrhythmogenic right ventricular cardiomyopathy and dilated cardiomyopathy. During the course of DSP cardiomyopathy, episodes of acute myocardial injury may occur. While their mechanisms remain unclear, myocarditis has been postulated as an underlying cause. We report on an adolescent girl with arrhythmogenic biventricular cardiomyopathy and three acute myocarditis-like episodes in whom we found a novel truncating DSP variant accompanied by a known low penetrance R490K variant in the NLRP3. Upon family screening, other carriers of the DSP variant have been identified in whom only mild cardiac abnormalities were found. We hypothesized that the uncommon course of cardiomyopathy in the proband as well as striking discrepancies in the phenotype observed in her family may be explained by the co-existence of her low penetrance genetic autoinflammatory predisposition.

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