A novel homozygous mutation in the TRDN gene causes a severe form of pediatric malignant ventricular arrhythmia.

摘要: Background Triadin is a protein expressed in cardiac and skeletal muscle that has an essential role the structure functional regulation of calcium release units excitation–contraction coupling. Mutations triadin gene (TRDN) have been described different forms human arrhythmia syndromes with early onset severe arrhythmogenic phenotype, including knockout syndrome. Objective The purpose this study was to characterize pathogenetic mechanism underlying case pediatric malignant associated defect TRDN gene. Methods We used trio whole exome sequencing approach identify genetic 2-year-old boy who had resuscitated from sudden arrest frequent episodes ventricular fibrillation family history positive for death. then performed in vitro analysis investigate possible pathogenic mechanisms phenotype. Results identified novel homozygous missense variant (p.L56P) proband inherited heterozygous unaffected parents. Expression green fluorescent (GFP)-tagged mutant isoform (TRISK32-L56P-GFP) heterologous systems revealed mutation alters dynamics. Furthermore, when co-expressed type 2 ryanodine receptor, caffeine-induced TRISK32-L56P-GFP relatively lower compared observed wild-type construct. Conclusion results allowed us hypothesize rare recessive form, suggesting potentially can trigger arrhythmias by altering homeostasis.