A Modern Approach to Classify Missense Mutations in Cardiac Channelopathy Genes

Abriel, Hugues; Zaklyazminskaya, E. V.

doi:10.1161/circgenetics.112.964809

Cited by 5 publications

(4 citation statements)

References 18 publications

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“…Firstly, it can be congenitally associated with mutations in the ion channels, which causes changes in ventricular repolarization [ 2 ]. Secondly, it can be acquired from medications such as certain antiarrhythmics, calcium agonists, antipsychotics, antihistamines, macrolide, fluoroquinolone antibiotics, some antifungals, and antiretroviral medications, which are known to prolong the QT interval by lengthening the repolarization phase of cardiac myocytes [ 3 , 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Salbutamol-Induced QT Interval Prolongation in a Two-Year-Old Patient

Elgassim¹,

Abdelrahman²,

Saied³

et al. 2022

Cureus

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Salbutamol-induced QT interval prolongation is a relatively rare adverse effect of beta2-agonists. We report a case of a two-year-old female patient with no known past medical history, brought by her parents to the ED 30 minutes after ingesting a total dose of 97 mg of salbutamol solution. ECG was done for the patient when she arrived and showed sinus tachycardia with prolonged QTc (509 ms) and normal QRS complex. The patient was admitted to the Pediatric Intensive Care Unit (PICU) with persistent tachycardia and tachypnea in the initial reassessment. ECG was repeated with normal QT interval after IV Mg sulfate. The patient was observed in PICU for 12 hours with serial ECG and venous blood gas (VBG). IV potassium chloride (KCL) infusion started, and serial VBG showed normal potassium and lactate. The patient was doing well in the next six hours, with normal serial ECG, labs, and vital signs. In conclusion, salbutamol-induced QT prolongation has infrequently been reported in the literature. Although inhaled salbutamol is commonly used in clinical practice, physicians have limited experience with the severe features of its toxicity. Salbutamol is known to cause minimal side effects, which may be under-recognized and progress to serious manifestations such as hypokalemia, QT prolongation, and sudden cardiac death.

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Section: Introductionmentioning

confidence: 99%

Salbutamol-Induced QT Interval Prolongation in a Two-Year-Old Patient

Elgassim¹,

Abdelrahman²,

Saied³

et al. 2022

Cureus

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“…Long QT syndrome (LQTS) is linked to mutations in the ion channels, which can lead to disturbances in ventricular repolarization . This condition puts patients at risk for syncope due to polymorphic ventricular tachycardia, typically torsades de pointes (TdP) which may deteriorate into ventricular fibrillation and cause sudden cardiac death (SCD) .…”

Section: Introductionmentioning

confidence: 99%

A case of long QT syndrome: challenges on a bumpy road

Magnusson

Gustafsson

2017

Clinical Case Reports

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“…Other recent studies have demonstrated that SCN5A is a polymorphic gene, and as a consequence, one of the main challenges for this field is to distinguish between rare but benign (silent SNPs) and pathogenic ones. There exist different approaches to address this clinically relevant question . However, molecular and biophysical characterization of Na v 1.5 channels that are heterologously expressed in mammalian cells remains one of the most informative methods to investigate the pathogenicity of naturally occurring variants.…”

Section: Introductionmentioning

confidence: 99%

“…There exist different approaches to address this clinically relevant question. 10 However, molecular and biophysical characterization of Na v 1.5 channels that are heterologously expressed in mammalian cells remains one of the most informative methods to investigate the pathogenicity of naturally occurring variants.…”

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confidence: 99%

Characterization of 2 Genetic Variants of Na_v1.5‐Arginine 689 Found in Patients with Cardiac Arrhythmias

Sottas

Rougier

Jousset

et al. 2013

Cardiovasc electrophysiol

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Nav1.5‐Arg689 in Arrhythmias Hundreds of genetic variants in SCN5A, the gene coding for the pore‐forming subunit of the cardiac sodium channel, Nav1.5, have been described in patients with cardiac channelopathies as well as in individuals from control cohorts. The aim of this study was to characterize the biophysical properties of 2 naturally occurring Nav1.5 variants, p.R689H and p.R689C, found in patients with cardiac arrhythmias and in control individuals. In addition, this study was motivated by the finding of the variant p.R689H in a family with sudden cardiac death (SCD) in children. When expressed in HEK293 cells, most of the sodium current (INa) biophysical properties of both variants were indistinguishable from the wild‐type (WT) channels. In both cases, however, an ∼2‐fold increase of the tetrodotoxin‐sensitive late INa was observed. Action potential simulations and reconstruction of pseudo‐ECGs demonstrated that such a subtle increase in the late INa may prolong the QT interval in a nonlinear fashion. In conclusion, despite the fact that the causality link between p.R689H and the phenotype of the studied family cannot be demonstrated, this study supports the notion that subtle alterations of Nav1.5 variants may increase the risk for cardiac arrhythmias.

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A Modern Approach to Classify Missense Mutations in Cardiac Channelopathy Genes

Cited by 5 publications

References 18 publications

Salbutamol-Induced QT Interval Prolongation in a Two-Year-Old Patient

Salbutamol-Induced QT Interval Prolongation in a Two-Year-Old Patient

A case of long QT syndrome: challenges on a bumpy road

Characterization of 2 Genetic Variants of Na_v1.5‐Arginine 689 Found in Patients with Cardiac Arrhythmias

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A Modern Approach to Classify Missense Mutations in Cardiac Channelopathy Genes

Cited by 5 publications

References 18 publications

Salbutamol-Induced QT Interval Prolongation in a Two-Year-Old Patient

Salbutamol-Induced QT Interval Prolongation in a Two-Year-Old Patient

A case of long QT syndrome: challenges on a bumpy road

Characterization of 2 Genetic Variants of Nav1.5‐Arginine 689 Found in Patients with Cardiac Arrhythmias

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Product

Resources

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Characterization of 2 Genetic Variants of Na_v1.5‐Arginine 689 Found in Patients with Cardiac Arrhythmias