LAUSR

Large deletions and duplications may be responsible for some of the cause of genetically elusive arrhythmia syndromes. Introduction Triadin is a transmembrane protein located in the sarcoplasmic reticulum; it interacts with both ryanodine (RYR2) and calsequestrin (CASQ2) to facilitate calcium homeostasis in the human cardiac and skeletal muscle cells. Pathogenic variants in the RYR2 and CASQ2 genes are more commonly associated with catecholaminergic polymorphic ventricular tachycardia (CPVT). Triadin is a more recently acknowledged protein, wherein genetic aberrations in triadin are responsible for a number of malignant arrhythmic syndromes, particularly in younger children. These triadin mutations are recessively inherited, and they are associated with a prolonged QT interval and T-wave abnormalities; the term “triadin knockout syndrome” has been suggested by Altmann and colleagues. The TRDN gene localizes to chromosome 6, and is seen in a variety of isoforms including Trisk 32, which is expressed predominantly in cardiac muscle. These isoforms are generated through alternative splicing of the triadin gene. The protein is composed of a transmembrane domain with both cytosolic and luminal components and is 286 amino acids long. Knockout of this gene in murine cardiac muscle causes a loss of calcium regulation, impaired excitation contraction coupling, and cardiac arrhythmia, particularly during betaadrenergic stimulation.