GENOTYPIC/PHENOTYPIC CHARACTERISTICS INJAPANESE PATIENTS WITH KCJVJ2-ASSOCIATEDANDERSEN-TAWIL SYNDROME

摘要

Background; ATS is a rare inherited disease with periodic paralysis, dysmorphic features, and ventricular tachyarrhythmias (VT) with QT-U prolongation (LQT7). Mutations in KCNJ2 cause the syndrome. Methods; We screened KCNJ2 in 13 patients from 7 unrelated Japanese ATS families and in 75 unrelated probands of long QT syndrome (LQTS). Results; Six KCNJ2 mutations were identified in ATS (G144S, G146S, T192A, G215D, R218W, and R218Q in 2 families) and two in LQTS (E118D and P351S). Functional assay of the novel G146S mutant displayed no functional currents and strong dominant negative suppression effects coexpressing with wild type. Two KCNJ2 mutations found in LQTS caused no functional change. Most of ATS patients carrying KCNJ2 mutation showed over 2 of triad for ATS. In ECG, we observed a variety of ventricular arrhythmias (bidirectional, polymorphic, and monomorphic VT and Vf). Two probands families experienced aborted sudden death presumably due to Vf. Predominant U waves were characteristic in 9 of 10 measurable carriers. Periodic paralysis was seen in 12 of 13 carriers (92%), dysmorphic features in 7 (54%), and seizures during infancy in 4 (31%). Conclusions; Our ATS patients appeared to show a high penetrance rate with typical cardiac phenotypes: predominant U wave and bidirectional VT.