Common Genotypes of Long QT Syndrome in China and the Role of ECG Prediction.
OBJECTIVE
Genetic testing, a gold standard for long QT syndrome (LQTS) diagnosis, is time-consuming and costly when all the 15 candidate genes are screened. Since genotype-specific ECG patterns are present in most LQT1-3 mutation carriers, we tested the utility of ECG-guided genotyping in a large cohort of Chinese LQTS patients.


RESULTS
We enrolled 230 patients (26 ± 17 years, 66% female) with a clinical diagnosis of LQTS. Genotypes were predicted as LQT1-3 based on the presence of ECG patterns typical for each genotype in 200 patients (85 LQT1, 110 LQT2 and 5 LQT3). Family-based genotype prediction was also conducted if gene-specific ECG patterns were found in other affected family members. Mutational screening identified 104 mutations (44% novel), i.e. 46 KCNQ1, 54 KCNH2 and 4 SCN5A mutations. The overall predictive accuracy of ECG-guided genotyping was 79% (157/200) and 79% (67/85), 78% (86/110) and 80% (4/5) for LQT1, LQT2 and LQT3, respectively. The predictive accuracy was 98% (42/43) when family-based ECG assessment was performed.


CONCLUSIONS
From this large-scale genotyping study, we found that LQT2 is the most common genotype among the Chinese. Family-based ECG-guided genotyping is highly accurate. ECG-guided genotyping is time- and cost-effective. We therefore recommend it as an optimal approach for the genetic diagnosis of LQTS.
Heart Center, Peking University People's Hospital, Beijing, PR China.
Yuanfeng
Y
Gao
Wenling
W
Liu
Cuilan
C
Li
Xiaoliang
X
Qiu
Xuguang
X
Qin
Baojing
B
Guo
Xueqin
X
Liu
Jianfeng
J
Li
Yue
Y
Yuan
Xiaomei
X
Li
Lu
L
Liang
Lei
L
Li
Kui
K
Hong
Jielin
J
Pu
Jinqiu
J
Liu
Qing
Q
Wang
Li
L
Zhang
Da-Yi
DY
Hu
D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics; D002681:China; D015331:Cohort Studies; D004562:Electrocardiography; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D008133:Long QT Syndrome / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012042:Registries; D055815:Young Adult
D051657:KCNQ1 Potassium Channel