Non‐dilated left ventricular cardiomyopathy with arrhythmias is commonly caused by the nonsense variant DSP:c.3793G>T in Slovenian patients

Abstract

AbstractDSP‐cardiomyopathy has recently been recognised as a specific type of cardiomyopathy. Using an in‐house Mendelian disease registry, we aimed to identify probands with likely pathogenic or pathogenic DSP variants. We detected these variants in 4.8% and 77.8% of genotype‐positive probands referred for dilated and non‐dilated left ventricular cardiomyopathy (NDLVC), respectively. We identified six Slovenian probands with the DSP:c.3793G>T and characterised them along with further eight of their relatives at the molecular and phenotypic level. Medical records revealed NDLVC with arrhythmia in six individuals (five probands, one relative; 33 ± 14 years; three males, three females). All had subepicardial late gadolinium enhancement on cardiac MRI (CMRI), and five received an ICD. Four individuals (one proband, three relatives; 48 ± 14 years; all female) had no ECG and/or cardiac abnormalities on CMRI detected. Our analysis presents a Slovenian‐specific molecular pathology of DSP cardiomyopathy, delineates the clinical manifestation of DSP:c.3793C>T, and thereby improves the understanding of the clinical outcomes associated with truncating DSP variants.