Scoring by "diagnostic effectiveness" highlighted that PLN should also be routinely screened besides historically validated genes for HCM and its mimics.
The CaMKII target pT17-phospholamban was 5.5-fold increased only in sarcomere-mutation HCM (P=0.01), as was autophosphorylated CaMKII (P<0.01), suggestive of constitutive activation.
Our aim was to screen 315 patients with arrhythmogenic right ventricular cardiomyopathy (n = 111), DCM (n = 95), hypertrophic cardiomyopathy (n = 40) and peripartum cardiomyopathy (n = 69) for disease-causing PLN mutations by high resolution melt analysis and DNA sequencing.
Among these are mutations in TNNC1- encoded cardiac troponin C, PLN-encoded phospholamban, and JPH2-encoded junctophilin 2 which have each been associated with HCM in multiple studies.
Compared with similar studies, we identified an overall yield of PLN-HCM mutations of 0.65%, similar to 3 genes that are part of current HCM genetic test panels.
PLN-encoded phospholamban mutation in a large cohort of hypertrophic cardiomyopathy cases: summary of the literature and implications for genetic testing.