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Genotype-based clinical manifestation and treatment of Chinese long QT syndrome patients with KCNQ1 mutations – R380S and W305L

  • Hui Zhou (a1), Wei Lai (a1), Wengen Zhu (a1), Jinyan Xie (a2), Xin Liu (a1), Yang Shen (a1), Ping Yuan (a1), Ying Liu (a1), Qin Cao (a2), Wenfeng He (a2) and Kui Hong (a1) (a2)...



Most long QT syndrome patients are associated with genetic mutations. We aimed to investigate the clinical and biochemical characteristics and look for genotype-based preventive implications in Chinese long QT syndrome patients.

Methods and results

We identified two missense mutations of the KCNQ1 gene in two independent Chinese families, including a previously reported mutation R380S in the C-terminus and a novel mutation W305L in the P-loop domain of the Kv7.1 channel, respectively. The proband with R380S was an 11-year-old girl who suffered a prolonged corrected QT interval of 660 ms, recurrent syncope, and sudden cardiac death, whose father was an asymptomatic carrier. The mutation W305L was detected in a 36-year-old woman with long QT syndrome and her immediate family members including the proband’s younger sister with an unexplained syncope, her son, and her elder daughter without symptoms. Metoprolol appeared to be effective in preventing arrhythmias and syncope in long QT syndrome patients with mutation W305L. Both R380S and W305L mutations led to “loss-of-function” of the Kv7.1 channel accounting for the clinical phenotypes.


We first show two missense KCNQ1 mutations – R380S and W305L – in Chinese long QT syndrome patients, resulting in the loss of protein function. Mutation W305L in the P-loop domain of the Kv7.1 may derive a pronounced benefit from β-blocker therapy in symptomatic long QT syndrome patients, whereas mutation R380S located in the C-terminus may be associated with a high risk of sudden cardiac death.


Corresponding author

Correspondence to: Dr K. Hong, MD, PhD, Cardiovascular Department, The Second Affiliated Hospital of Nanchang University, Jiangxi 330006, China. Tel: +00 867 918 631 2917; Fax: +00 867 918 626 2262; E-mail:


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Co-first authors: Hui Zhou and Wei Lai.



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