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Updated: Jun 24, 2025

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
LV-predominant arrhythmogenic cardiomyopathy related to pathogenic DSP-variant
Soban Ahmad1, Husam El Sharu1, Robin Fernandes2
1Department of Internal Medicine East Carolina University Greenville North Carolina USA.
Key Clinical Message:
In contrast to previously thought, arrhythmogenic cardiomyopathy can occur exclusively in the left ventricle in association with autosomal dominant mutation, even without any skin manifestations.
Abstract:
We present a case of a 43-year-old male with left ventricle (LV)-predominant arrhythmogenic cardiomyopathy (ACM) caused by a novel p.Q1830 mutation in the desmoplakin (DSP) gene. The patient had a significant family history of sudden cardiac death (SCD) and presented with presyncope and exertional dyspnea. The patient's electrocardiography (ECG) showed frequent premature ventricular complexes (PVCs) with bigeminy and couplet patterns. Cardiac magnetic resonance imaging (CMR) revealed late gadolinium enhancement of the left ventricle (LV) and ventricular systolic dysfunction, suggesting LV-predominant arrhythmogenic cardiomyopathy. The patient was started on guideline-directed medical therapy (GDMT), and an implantable cardioverter-defibrillator (ICD) was implanted for primary prevention. The patient reported significant improvement in his heart failure symptoms at the 2-year follow-up. The article highlights the importance of timely diagnosis with multimodality imaging and genetic testing and management of the rare DSP-related LV-predominant ACM associated with a high risk of SCD.
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