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

Mono-allelic dominant mutations in the desmoplakin gene () have been linked to known cardiac disorders, such as arrhythmogenic right ventricular cardiomyopathy and dilated cardiomyopathy. During the course of 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 variant accompanied by a known low penetrance R490K variant in the . Upon family screening, other carriers of the 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.