Introduction: Recent data showed that long QT syndrome (LQTS) patients with mutations in the pore region of the HERG (LQT2) gene have significantly higher risk of cardiac events than subjects with mutations in the non‐pore region. The aim of this study was to determine whether there is an association between the location of mutations in the KCNQ1 gene and cardiac events in LQT1 patients.

Methods and Results: The study population consisted of 294 LQT1 patients with KCNQ1 gene mutations. Demographic, clinical, and follow‐up information was compared among subjects with different locations of KCNQ1 mutations defined as pre‐pore region including N‐terminus (1–278), pore region (279–354), and post‐pore region including C‐terminus (>354). Cardiac events observed during follow‐up from birth until age of last contact or age 40 years were defined as syncope, cardiac arrest, or sudden death. There were 164 (56%) LQT1 patients with pre‐pore mutations, 101 (34%) with pore mutations, and 29 (10%) with post‐pore mutations. QTc duration did not differ significantly among the three subgroups (mean QTc = 494, 487, and 501 ms, respectively). There was no significant difference between groups with regard to the risk of cardiac events by age 40 years.

Conclusion: There are no significant differences in clinical presentation, ECG parameters, and cardiac events among LQT1 patients with different locations of KCNQ1 mutations. These findings indicate that factors other than location of mutation influence clinical phenotype in patients with LQT1 mutations. (J Cardiovasc Electrophysiol, Vol. 14, pp. 1149‐1153, November 2003)