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

Figures

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  Figure 1. Changes in the troponin T concentration, reflecting the course of the DSP cardiomyopathy with recurrent acute myocardial injury. A dotted line was used where no measurements were available to recreate the course of the variable.

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  Figure 2. 12-lead electrocardiogram recordings in the proband with desmoplakin cardiomyopathy. (A) Abnormalities of QRS complex: low voltage, prolonged terminal activation duration in lead V1 (see in the magnified box), fragmentations in leads II, III and aVF; (B) multifocal premature ventricular contractions: (1) left bundle branch block (LBBB)-like morphology (QRS transition zone V3) with inferior axis suggests the beginning of activation in the right ventricular outflow tract, (2) LBBB-like morphology (QRS transition zone in V6) with superior axis suggests the origin from the free wall of the right ventricle, periapically; (3) nonspecific intraventricular conduction delay-like morphology (QRS transition zone in V1–2) with inferior axis suggests the beginning of activation in the left ventricular outflow tract.

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  Figure 3. Cardiac magnetic resonance images consistent with the diagnosis of arrhythmogenic cardiomyopathy. (A) Short-axis slice demonstrating moderate sub-epicardial and mid-wall areas of late gadolinium enhancement with a ring-like pattern (arrows); (B) the progression of ring-like pattern fibrosis (arrows) in comparison to the study performed 3 years earlier; (C) steady-state free precession 4-chamber view in the end-diastole; (D) steady-state free precession 4-chamber view in end-systole. Areas of bulging of right ventricular wall are seen.

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  Figure 4. Integrated Genomic Viewer (IGV) views and electropherograms of the identified heterozygous variants: DSP NM_004415.4:c.3737dupA (p.Asn1246LysfsTer7), PKP2 NM_004572.3:c.2636T>C (p.Leu879Pro), and NLRP3 NM_004895.4:c.1469G>A (p.Arg490Lys).

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  Figure 5. The results of genetic screening for the identified variants, shown on a pedigree. Squares represent males and circles represent females. The arrow denotes the proband. The solid black symbol denotes arrhythmogenic cardiomyopathy. Open symbols denote unaffected individuals. Legend: wt—wild type, var—heterozygous variants: DSP—NM_004415.4:c.3737dupA (p.Asn1246LysfsTer7) variant in the desmoplakin gene, PKP2—NM_004572.3:c.2636T>C (p.Leu879Pro) variant in the plakophilin-2 gene, NRLP3—NM_004895.4:c.1469G>A (p.Arg490Lys) variant in the NLR Family Pyrin Domain Containing 3 gene.