UNVEILING THE DARK SIDE OF PHOSPHOLAMBAN: THE ROLE OF CASCADE GENETIC TESTING

Intracellular Ca²+ regulation is critical for cardiac function, with SERCA2a pumping Ca²+back into the sarcoplasmic reticulum for relaxation, counteracted by its reversible inhibitor phospholamban (PLN). Mutations in PLN, such as p.Leu39X, profoundly affect cardiac health. Homozygosity for Leu39X, described only twice in Greece (2001), is extremely rare and causes early–onset dilated cardiomyopathy (DCM) and heart failure, often requiring transplantation by the third decade. Heterozygotes display incomplete penetrance, with outcomes ranging from normal function to left ventricular hypertrophy or DCM.