Genetic homozygosity in a diverse population: An experience of long QT syndrome

Mahdieh, Nejat; Khorgami, Mohammadrafi; Soveizi, Mahdieh; Aliakbar, Saranaz Seyed; Dalili, Mohammad; Rabbani, Bahareh

doi:10.1016/j.ijcard.2020.05.056

Cited by 4 publications

(3 citation statements)

References 38 publications

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“…However, other major genes might exist in some populations. For instance, in our previous study, we demonstrated that the common genes of LQT syndromes were responsible for only 43% of patients in a sample of the Iranian population [ 5 ]. Here, we describe an Iranian child suffering from syncope without stress and with a minimum Schwartz score of 3.5 due to a novel nonsense variant in KCNQ1 .…”

Section: Discussionmentioning

confidence: 99%

“…Nonsense variants account for a lower percentage of point mutations in KCNQ1 , with approximately 10% of KCNQ1 variants being nonsense [ 5 ]. In the present study, we found a novel nonsense variant, c.968G > A, leading to p.Trp323Ter in KCNQ1 in an Iranian proband whose brother and mother were also symptomatic.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously described the genetic spectrum of the common types of LQT syndromes in our population. [ 5 , 8 , 17 ]. Here, we report a novel stop-gain pathogenic variant in KCNQ1 causing LQT1 in an Iranian child.…”

Section: Introductionmentioning

confidence: 99%

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A novel stop-gain pathogenic variant in the KCNQ1 gene causing long QT syndrome 1

et al. 2023

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Background Inherited primary arrhythmias, such as long QT (LQT) syndromes, are electrical abnormalities of the heart mainly due to variants in 3 genes. We herein describe a novel stop-gain pathogenic variant in the KCNQ1 gene in an Iranian child with LQT syndrome 1. Methods The patient and his family underwent clinical evaluation, electrocardiographic Holter monitoring, and whole-exome sequencing. Sanger sequencing and segregation analysis were used to confirm the variant in the patient and his family, respectively. The pathogenicity of the variant was checked via an in silico analysis. Results The proband suffered from bradycardia and had experienced syncope without stress. The corrected QT interval was 470 ms (the Schwartz score ≥ 3.5), and the Holter monitoring showed sinus rhythm, infrequent premature atrial contractions, and a prolonged QT interval in some leads. Whole-exome and Sanger sequencing showed c.968G > A in 3 affected family members. According to the American College of Medical Genetics and Genomics criteria, c.968G > A was classified as a pathogenic variant. Conclusions The KCNQ1 gene is the main cause of LQT syndromes in our population. The common genes of LQT syndromes should be studied in our country’s different ethnicities to determine the exact role of these genes in these subpopulations.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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A novel stop-gain pathogenic variant in the KCNQ1 gene causing long QT syndrome 1

et al. 2023

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Genetics of Cardiovascular Disease and Applications of Genetic Testing

Mahdieh

Rabbani

Maleki

2022

Practical Cardiology

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Computational analysis of long QT syndrome type 2 and the therapeutic effects of KCNQ1 antibodies

Pan,

Fu,

Jiang

et al. 2024

DIGITAL HEALTH

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Objective Long QT interval syndrome (LQTS) is a highly dangerous cardiac disease that can lead to sudden cardiac death; however, its underlying mechanism remains largely unknown. This study is conceived to investigate the impact of two general genotypes of LQTS type 2, and also the therapeutic effects of an emerging immunology-based treatment named KCNQ1 antibody. Methods A multiscale virtual heart is developed, which contains multiple biological levels ranging from ion channels to a three-dimensional cardiac structure with realistic geometry. Critical biomarkers at different biological levels are monitored to investigate the remodeling of cardiac electrophysiology induced by mutations. Results Simulations revealed multiple important mechanisms that are hard to capture via conventional clinical techniques, including the augmented dispersion of repolarization, the increased vulnerability to arrhythmias, the impaired adaptability in tissue to high heart rates, and so on. An emerging KCNQ1 antibody-based therapy could rescue the prolonged QT interval but did not reduce the vulnerable window. Conclusions Tiny molecular alterations can lead to cardiac electrophysiological remodeling at multiple biological levels, which in turn contributes to higher susceptibility to lethal arrhythmias in long QT syndrome type 2 patients. The KCNQ1 antibody-based therapy has proarrhythmic risks notwithstanding its QT-rescuing effects.

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Genetic homozygosity in a diverse population: An experience of long QT syndrome

Cited by 4 publications

References 38 publications

A novel stop-gain pathogenic variant in the KCNQ1 gene causing long QT syndrome 1

A novel stop-gain pathogenic variant in the KCNQ1 gene causing long QT syndrome 1

Genetics of Cardiovascular Disease and Applications of Genetic Testing

Computational analysis of long QT syndrome type 2 and the therapeutic effects of KCNQ1 antibodies

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