Background: Mutations in the PRKAG2 gene have been shown to cause Wolff-Parkinson-White (WPW) syndrome associated with hypertrophic cardiomyopathy. Among them, a missense mutation, Arg531Gly of PRKAG2, was identified in familial WPW syndrome without cardiac hypertrophy. However, there is not much data of mutation in the PRKAG2 gene in sporadic WPW syndrome Methods and Results: We evaluated the C to G substitution at nucleotide 1681 in axon 15 of PRKAG2 leading to the new Arg 531 to Gly missense mutation in sporadic WPW syndrome. We enrolled the eighty-one patients, who underwent electrophysiologic study and catheter ablation due to WPW syndrome. The same site was analyzed in 90 subjects without WPW syndrome as control. Pyrosequencing and RFLP were used to search for PRKAG2 mutation. All patients with WPW syndrome did not show the Arg531Gly missense mutation of PRKAG2. We did not find this mutation in control subjects also. Conclusion: This study suggests that, unlike familial WPW syndrome, a missense mutation, Arg531Gly of PRKAG2 may not be associated with sporadic WPW syndrome. Further studies are needed to find the molecular basis of sporadic WPW syndrome