BACKGROUND: Mutations of KCNJ2, the gene encoding the human inward rectifier 
potassium channel Kir2.1, cause Andersen-Tawil syndrome (ATS), a disease 
exhibiting ventricular arrhythmia, periodic paralysis, and dysmorphic features. 
However, some KCNJ2 mutation carriers lack the ATS triad and sometimes share the 
phenotype of catecholaminergic polymorphic ventricular tachycardia (CPVT). We 
investigated clinical and biophysical characteristics of KCNJ2 mutation carriers 
with "atypical ATS."
METHODS AND RESULTS: Mutational analyses of KCNJ2 were performed in 57 unrelated 
probands showing typical (≥2 ATS features) and atypical (only 1 of the ATS 
features or CPVT) ATS. We identified 24 mutation carriers. Mutation-positive 
rates were 75% (15/20) in typical ATS, 71% (5/7) in cardiac phenotype alone, 
100% (2/2) in periodic paralysis, and 7% (2/28) in CPVT. We divided all carriers 
(n=45, including family members) into 2 groups: typical ATS (A) (n=21, 47%) and 
atypical phenotype (B) (n=24, 53%). Patients in (A) had a longer QUc interval 
[(A): 695 ± 52 versus (B): 643 ± 35 ms] and higher U-wave amplitude (0.24 ± 0.07 
versus 0.18 ± 0.08 mV). C-terminal mutations were more frequent in (A) (85% 
versus 38%, P<0.05). There were no significant differences in incidences of 
ventricular tachyarrhythmias. Functional analyses of 4 mutations found in (B) 
revealed that R82Q, R82W, and G144D exerted strong dominant negative suppression 
(current reduction by 95%, 97%, and 96%, respectively, versus WT at -50 mV) and 
T305S moderate suppression (reduction by 89%).
CONCLUSIONS: KCNJ2 gene screening in atypical ATS phenotypes is of clinical 
importance because more than half of mutation carriers express atypical 
phenotypes, despite their arrhythmia severity.