Find in Library

Left ventricular non-compaction cardiomyopathy (LVNC) is a rare heart disease, with or without left ventricular dysfunction, which is characterized by a two-layer structure of the myocardium and an increased number of trabeculae. The study of familial forms of LVNC is helpful for risk prediction and genetic counseling of relatives. Here, we present a family consisting of three members with LVNC. Using a next-generation sequencing approach a combination of two (likely) pathogenic nonsense mutations <i>DSG2</i>-p.S363X and <i>TBX20</i>-p.D278X was identified in all three patients. <i>TBX20</i> encodes the cardiac T-box transcription factor 20. <i>DSG2</i> encodes desmoglein–2, which is part of the cardiac desmosomes and belongs to the cadherin family. Since the identified nonsense variant (<i>DSG2</i>-p.S363X) is localized in the extracellular domain of <i>DSG2</i>, we performed in vitro cell transfection experiments. These experiments revealed the absence of truncated <i>DSG2</i> at the plasma membrane, supporting the pathogenic relevance of <i>DSG2</i>-p.S363X. In conclusion, we suggest that in the future, these findings might be helpful for genetic screening and counseling of patients with LVNC.