Mutation Analysis of KCNQ1, KCNH2 and SCN5A Genes in Taiwanese Long QT Syndrome Patients

Chang, Ya‐Sian; Yang, Yiwen; Lin, Yen‐Nien; Lin, Kuo‐Hung; Chang, Kuan‐Cheng; Chang, Jan‐Gowth

doi:10.1536/ihj.14-428

Cited by 8 publications

(7 citation statements)

References 30 publications

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“…Those with mutation in each of these particular gene have different clinical characteristics and are associated with different triggering events for arrhythmia as well as response to treatment [ 6 ]. There were reports on various gene mutation frequency in Asian countries [ [7] , [8] , [9] , [10] , [11] , [12] ]. From a previous study in Thai children, the ratio of LQTS patients who had cardiac events at rest or sleep appeared to be higher than those found in other Asian countries [ 13 ].…”

Section: Introductionmentioning

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: Introductionmentioning

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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“…Common symptoms include syncope, seizures, and polymorphic ventricular tachyarrhythmias, that may lead to sudden cardiac death [4] . Among all types of LQTS, Long QT types 1–3 (LQT 1–3) constitute about 75% of the cases [5] , [6] . LQT1 is also observed as an autosomal recessive trait in patients with sensorineural deafness [Jervell-Lange Nielsen syndrome (JLNS)], whereas patients without deafness are referred to as autosomal recessive Romano-Ward syndrome (AR RWS) [7] .…”

Section: Introductionmentioning

confidence: 99%

Phenotype guided characterization and molecular analysis of Indian patients with long QT syndromes

Vyas

Puri

Namboodiri

et al. 2016

Indian Pacing and Electrophysiology Journal

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BackgroundLong QT syndromes (LQTS) are characterized by prolonged QTc interval on electrocardiogram (ECG) and manifest with syncope, seizures or sudden cardiac death. Long QT 1–3 constitute about 75% of all inherited LQTS. We classified a cohort of Indian patients for the common LQTS based on T wave morphology and triggering factors to prioritize the gene to be tested. We sought to identify the causative mutations and mutation spectrum, perform genotype-phenotype correlation and screen family members.MethodsThirty patients who fulfilled the criteria were enrolled. The most probable candidate gene among KCNQ1, KCNH2 and SCN5A were sequenced.ResultsOf the 30 patients, 22 were classified at LQT1, two as LQT2 and six as LQT3. Mutations in KCNQ1 were identified in 17 (77%) of 22 LQT1 patients, KCNH2 mutation in one of two LQT2 and SCN5A mutations in two of six LQT3 patients. We correlated the presence of the specific ECG morphology in all mutation positive cases. Eight mutations in KCNQ1 and one in SCN5A were novel and predicted to be pathogenic by in-silico analysis. Of all parents with heterozygous mutations, 24 (92%) of 26 were asymptomatic. Ten available siblings of nine probands were screened and three were homozygous and symptomatic, five heterozygous and asymptomatic.ConclusionsThis study in a cohort of Asian Indian patients highlights the mutation spectrum of common Long QT syndromes. The clinical utility for prevention of unexplained sudden cardiac deaths is an important sequel to identification of the mutation in at-risk family members.

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“…33) Approximately 70-75% of LQTS patients have mutations in one of the 3 major LQTS-causing genes (KCNQ1, KCNH2 and SCN5A), the result of which is that a genetic diagnosis cannot be established in 25-30% of patients. 34) In our study, the mutation detection rate was 44% (4/9 probands) even with application of NGS for 14 LQTS-related genes; this is unlikely to reflect the real genetic variant distribution in Russian patients because of the small number of subjects.…”

Section: Discussionmentioning

confidence: 55%

Gene-Targeted Analysis of Clinically Diagnosed Long QT Russian Families

Maltese¹,

Orlova

Красикова

et al. 2017

Int. Heart J.

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SummaryLong QT syndrome (LQTS) has great genetic heterogeneity: more than 500 mutations have been described in several genes. Despite many advances, a genetic diagnosis still cannot be established in 25-30% of patients. The aim of the present study was to perform genetic evaluation in 9 Russian families with LQTS; here we report the results of 4 positive probands and their relatives (a total of 16 individuals). All subjects underwent clinical examination, 12-lead ECG, and Holter monitoring. Genetic analysis of the 14 genes mainly involved in LQTS was performed using a next-generation sequencing approach. We identified two new mutations (KCNQ1 gene) and 6 known mutations (AKAP9, ANK2, KCNE1 and KCNJ2 genes) in 4 out of 9 probands, some of which have already been described in association with LQTS. Segregation studies suggest a possible causative role for KCNQ1 p.(Leu342Pro), AKAP9 p.(Arg1609Lys), KCNE1 p.(Asp85Asn), and KCNJ2 p.(Arg82Gln) variations. Our study confirmed the high genetic heterogeneity of this disease and highlights the difficulties to reveal clear pathogenic genotypes also in large pedigrees. To the best of our knowledge, this is the first genetic study of LQTS patients from Russian families. (Int Heart J 2017; 58: 81-87)

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Mutation Analysis of KCNQ1, KCNH2 and SCN5A Genes in Taiwanese Long QT Syndrome Patients

Cited by 8 publications

References 30 publications

Genotype and clinical characteristics of congenital long QT syndrome in Thailand

Genotype and clinical characteristics of congenital long QT syndrome in Thailand

Phenotype guided characterization and molecular analysis of Indian patients with long QT syndromes

Gene-Targeted Analysis of Clinically Diagnosed Long QT Russian Families

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