Common Genotypes of Long QT Syndrome in China and the Role of ECG Prediction

Gao, Yuanfeng; Liu, Wenjun; Li, Cuilan; Qiu, Xiaoliang; Qin, Xiaoping; Guo, Bin; Liu, Xueqin; Li, Jianfeng; Yuan, Yue; Li, Xiaomei; Lu, Liang; Li, Lei; Hong, Kui; Pu, Jielin; Liu, Jinqiu; Wang, Qing Kenneth; Zhang, Li; Hu, Da Yi

doi:10.1159/000440608

Cited by 16 publications

(17 citation statements)

References 23 publications

(27 reference statements)

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“…Of the 17 genes, most (75%) of the LQTS patients had pathogenic mutation in only one of the 3 genes: KCNQ1 (30–35%), KCNH2 (25–30%), and SCN5A (5–10%) [ 20 , 21 ]. There are few studies on the percentage of each type of LQTS in East Asian countries [ 8 , 11 , 12 , [22] , [23] , [24] ], as shown in Table 4 . Similar to the Western countries, the majority of the East Asian patients had LQT1, and LQT2.…”

Section: Discussionmentioning

confidence: 99%

Genotype and clinical characteristics of congenital long QT syndrome in Thailand

Saprungruang

Khongphatthanayothin

Mauleekoonphairoj

et al. 2018

Indian Pacing and Electrophysiology Journal

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BackgroundCongenital long QT syndrome (LQTS) is an inheritable arrhythmic disorder which is linked to at least 17 genes. The clinical characteristics and genetic mutations may be variable among different population groups and they have not yet been studied in Thai population.MethodsClinical characteristics were retrospectively reviewed from children and young adults with congenital long QT syndrome whose blood samples were sent for genotyping during 1998–2017. Sangers sequencing was used to sequentially identify KCNQ1 or KCNH2 genetic variants. Whole exome sequencing (WES) was used to identify variants in all other known LQTS genes.ResultsOf the 20 subjects (17 families), 45% were male, mean QTc was 550.3 ± 68.8 msec (range 470–731 msec) and total Schwartz's score was 5.6 ± 1.2 points (range 3–8 points). Fifty percent of patients had events at rest, 30% had symptoms after adrenergic mediated events, and 20% were asymptomatic. We discovered pathogenic and likely pathogenic genetic variants in KCNQ1, KCNH2, and SCN5A in 6 (35%), 4 (24%), and 2 (12%) families, respectively. One additional patient had variance of unknown significance (VUS) in KCNH2 and another one in ANK2. No pathogenic genetic variant was found in 3 patients (18%). Most patients received beta-blocker and 9 (45%) had ICD implanted. LQT1 patients were either asymptomatic or had stress-induced arrhythmia. Most of the LQT2 and LQT3 patients developed symptoms at rest or during sleep.ConclusionsOur patients with LQTS were mostly symptomatic at presentation. The genetic mutations were predominantly in LQT1, LQT2, and LQT3 genes.

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Section: Discussionmentioning

confidence: 99%

Genotype and clinical characteristics of congenital long QT syndrome in Thailand

Saprungruang

Khongphatthanayothin

Mauleekoonphairoj

et al. 2018

Indian Pacing and Electrophysiology Journal

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“…It is conceivable that with a more precise clinical definition, for example, if the analysis were limited to LQTS patients, the percentage of patients positive for these mutations would be expected to be much higher. In fact, in a Chinese cohort of 230 LQTS patients, 81% were found to be carriers of mutations in the three genes based on ECG‐guided genotyping (Gao et al., ).…”

Section: Discussionmentioning

confidence: 99%

Variant frequencies of KCNQ1, KCNH2, and SCN5A in a Chinese inherited arrhythmia cohort and other disease cohorts undergoing genetic testing

Liu

Bai

2019

Annals of Human Genetics

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KCNQ1, KCNH2, and SCN5A are the most common genes responsible for long QT syndrome and Brugada syndrome. However, the genetic variant frequencies of the three genes in different Chinese disease cohorts are largely unknown. In this study, we analyzed the genetic variants of KCNQ1, KCNH2, and SCN5A in patients from seven cohorts (total N = 11945, including patients clinically suspected to have inherited arrhythmia [n = 122], other cardiovascular diseases [n = 1045], epilepsy [n = 4797], or other diseases [n = 5841], and healthy controls [n = 140]) who had undergone genetic testing. All of these variants were identified via genetic testing by two Chinese companies using the Hi-Seq 2000 platform. A total of 1018 variants (minor allele frequency <0.01) were identified, with 186 (18%), 374 (37%), and 458 (46%) variants in the coding exons of KCNQ1, KCNH2, and SCN5A, respectively. Of these variants, 84% had unknown or uncertain clinical significance. The frequency of identified Clin-Var pathological/likely pathological variants was higher for KCNQ1 (13/186, 7.0%)than for KCNH2 (6/374, 1.6%) or SCN5A (10/458, 2.2%), and KCNH2 held the highest number and proportion of radical mutations (30/374, 8%). The prevalence of variants was highest in the inherited arrhythmia cohort (35%) and lowest in the healthy controls (<4%), as expected. Noticeably, the variant prevalence was relatively high in the epilepsy cohort (27%). Finally, only 22 of the 82 variants (26%) identified by both companies had consistent interpretations of pathogenicity between the two companies. Our study demonstrated a comprehensive spectrum of variants in KCNQ1, KCNH2, and SCN5A in a large number of Chinese individuals, including inherited arrhythmia, cardiovascular diseases, and epilepsy. The detailed variant frequency data of each cohort could serve as a valuable reference to facilitate further variant classification by others. We also found that the interpretations of pathogenicity differed greatly among the companies.

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“…In a recent single-centre study of LQTS in China, LQT2 was also the most common genotype. 18 We also identified five (8.5%) patients with rare CACNA1C (LQT8) mutations, all of whom were Hong Kong Chinese. Without a study of a large Chinese population in the past 5 years for cross reference, we cannot be certain whether LQT8 is more prevalent in Chinese than in other ethnic groups.…”

Section: Long Qt Syndrome Genotypementioning

confidence: 99%

Clinical and genetic profile of congenital long QT syndrome in Hong Kong: a 20-year experience in paediatrics

Kwok¹,

Liu²,

Chan³

et al. 2018

Hong Kong Med J

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Congenital long QT syndrome (LQTS) is a genetically transmitted cardiac channelopathy that can lead to sudden cardiac death. This study aimed to report the clinical and genetic characteristics of all young patients diagnosed with LQTS in the only tertiary paediatric cardiology centre in Hong Kong. Methods: This is a retrospective review of all paediatric and young adult patients diagnosed at our centre with LQTS from January 1997 to December 2016. The diagnosis of LQTS was established with a corrected QT interval (QTc) ≥480 ms, Schwartz score of >3 points, or the presence of a pathogenic mutation. Results: Fifty-nine patients (33 males) from 52 families were included, with a mean age of 8.17 years (range, 0.00-16.95 years) at presentation. Five patients had concomitant congenital heart diseases. The mean follow-up duration was 5.33 ± 4.65 years. The mean QTc in the cohort was 504 ± 47 ms. They presented with syncope and convulsion (49%), cardiac arrest (10%), bradycardia and neonatal atrioventricular block (12%). Fifteen (25%) patients were asymptomatic at diagnosis. Thirty-eight (64.4%) patients were confirmed to have a pathogenic mutation for LQTS genes. Forty-five (76.3%) patients received beta blocker therapy. Thirteen

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Common Genotypes of Long QT Syndrome in China and the Role of ECG Prediction

Cited by 16 publications

References 23 publications

Genotype and clinical characteristics of congenital long QT syndrome in Thailand

Genotype and clinical characteristics of congenital long QT syndrome in Thailand

Variant frequencies of KCNQ1, KCNH2, and SCN5A in a Chinese inherited arrhythmia cohort and other disease cohorts undergoing genetic testing

Clinical and genetic profile of congenital long QT syndrome in Hong Kong: a 20-year experience in paediatrics

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