Genotype-based clinical manifestation and treatment of Chinese long QT syndrome patients with KCNQ1 mutations - R380S and W305L.
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.
1Cardiovascular Department,The Second Affiliated Hospital of Nanchang University,Nanchang,China.
Hui
H
Zhou
1Cardiovascular Department,The Second Affiliated Hospital of Nanchang University,Nanchang,China.
Wei
W
Lai
1Cardiovascular Department,The Second Affiliated Hospital of Nanchang University,Nanchang,China.
Wengen
W
Zhu
2The Key Laboratory of Molecular Medicine,The Second Affiliated Hospital of Nanchang University,Nanchang,China.
Jinyan
J
Xie
1Cardiovascular Department,The Second Affiliated Hospital of Nanchang University,Nanchang,China.
Xin
X
Liu
1Cardiovascular Department,The Second Affiliated Hospital of Nanchang University,Nanchang,China.
Yang
Y
Shen
1Cardiovascular Department,The Second Affiliated Hospital of Nanchang University,Nanchang,China.
Ping
P
Yuan
1Cardiovascular Department,The Second Affiliated Hospital of Nanchang University,Nanchang,China.
Ying
Y
Liu
2The Key Laboratory of Molecular Medicine,The Second Affiliated Hospital of Nanchang University,Nanchang,China.
Qin
Q
Cao
2The Key Laboratory of Molecular Medicine,The Second Affiliated Hospital of Nanchang University,Nanchang,China.
Wenfeng
W
He
1Cardiovascular Department,The Second Affiliated Hospital of Nanchang University,Nanchang,China.
Kui
K
Hong
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D044466:Asian People; D002648:Child; D004562:Electrocardiography; D005260:Female; D005838:Genotype; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D008133:Long QT Syndrome / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D009154:Mutation; D010375:Pedigree; D055815:Young Adult
D000319:Adrenergic beta-Antagonists; D051657:KCNQ1 Potassium Channel
KCNQ1; Kv7.1; genetic testing; long QT syndrome; β-blocker