Elucidation of ALG10B as a Novel Long-QT Syndrome–Susceptibility Gene

Long-QT syndrome (LQTS) is characterized by QT prolongation and an increased risk for syncope, seizures, and sudden cardiac death. Most LQTS stem from pathogenic mutations in KCNQ1, KCNH2, or SCN5A. However, ≈10% of patients with LQTS remain genetically elusive. The authors identified a previously unknown gene that causes long-QT syndrome (LQTS), a heart condition that increases the risk of sudden cardiac death. The gene, ALG10B, was found to be responsible for the defective trafficking of the HERG protein, which plays a critical role in the heart's electrical activity. This defect results in prolonged action potential duration, triggering abnormal heart rhythms. The study suggests that ALG10B mutation analysis should be considered in patients with an LQT2-like phenotype who have tested negative for mutations in the known LQTS genes.