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

Published online by Cambridge University Press:  07 September 2015

Hui Zhou ,
Wei Lai ,
Wengen Zhu ,
Jinyan Xie ,
Xin Liu ,
Yang Shen ,
Ping Yuan ,
Ying Liu ,
Qin Cao  and
Wenfeng He
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Hui Zhou
Affiliation:
Cardiovascular Department, The Second Affiliated Hospital of Nanchang University, Nanchang, China
Wei Lai
Affiliation:
Cardiovascular Department, The Second Affiliated Hospital of Nanchang University, Nanchang, China
Wengen Zhu
Affiliation:
Cardiovascular Department, The Second Affiliated Hospital of Nanchang University, Nanchang, China
Jinyan Xie
Affiliation:
The Key Laboratory of Molecular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, China
Xin Liu
Affiliation:
Cardiovascular Department, The Second Affiliated Hospital of Nanchang University, Nanchang, China
Yang Shen
Affiliation:
Cardiovascular Department, The Second Affiliated Hospital of Nanchang University, Nanchang, China
Ping Yuan
Affiliation:
Cardiovascular Department, The Second Affiliated Hospital of Nanchang University, Nanchang, China
Ying Liu
Affiliation:
Cardiovascular Department, The Second Affiliated Hospital of Nanchang University, Nanchang, China
Qin Cao
Affiliation:
The Key Laboratory of Molecular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, China
Wenfeng He
Affiliation:
The Key Laboratory of Molecular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, China
Kui Hong*
Affiliation:
Cardiovascular Department, The Second Affiliated Hospital of Nanchang University, Nanchang, China The Key Laboratory of Molecular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, China
*
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: hongkui88@163.com
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Abstract

Aim

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.

Conclusions

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.

Keywords

long QT syndromeKCNQ1Kv7.1β-blockergenetic testing
Type
Original Articles
Information
Cardiology in the Young , Volume 26 , Issue 4 , April 2016 , pp. 754 - 763
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Copyright
© Cambridge University Press 2015 

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Footnotes

*

Co-first authors: Hui Zhou and Wei Lai.

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