Clinical Polymorphisms and Approaches of Arrhythmias Treatment in a Family with p.delKPQ1505-1507 Deletion in SCN5A Gene

Saber, Siamak; Houshmand, Massoud; Eftekhharzadeh, M; Nasab, Samiei; Fazelifar, Amirfarjam; Haghjoo, Majid; Заклязьминская, Е. В.; Гавриленко, А. В.

doi:10.15690/vramn.v69i5-6.1044

Cited by 2 publications

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References 33 publications

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“…Additional next generation sequencing analyses revealed the p.R25W mutation in KCNH2 gene in SCN5A ‐negative BrS patient. We also reported a known mutation p.delKPQ 1505‐1507 in SCN5A gene in another Iranian family who display not only BrS phenotype but also some of the carriers of this mutation had LQTS phenotype 11 …”

Section: Resultsmentioning

confidence: 66%

Brugada syndrome in Iran: Insights from a 12‐year longitudinal study

Haghjoo,

Askarinejad,

Madadi

et al. 2024

Cardiovasc electrophysiol

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BackgroundBrugada syndrome (BrS) is characterized by ST‐segment elevation in the right precordial leads, which is not explained by ischemia, electrolyte disturbances, or obvious structural heart disease.AimIn present study, we aim to evaluate presentation, long‐term outcome, genetic findings, and therapeutic interventions in patients with BrS.MethodsBetween September 2001 and June 2022, all consecutive patients with diagnosis of BrS were enrolled in the present study. All patients gave written informed consent for the procedure, and the local ethical committee approved the study.ResultsOf the 76 cases, 79% were proband and 21% were detected during screening after diagnosis of BrS in a family member. Thirty‐three (43%) patients had a typical spontaneous electrocardiogram (ECG) pattern. Thirty percent of the patients were symptomatic; symptomatic patients were more likely to have spontaneous type 1 Brugada ECG pattern in their ECGs (p = .01), longer PR interval (p = .03), and SCN5A mutation (p = .01) than asymptomatic patients. The mean PR interval was considerably longer in men than women (p = .034). SCN5A mutation was found in 9 out of 50 (18%) studied patients. Fifteen percent received appropriate implantable cardioverter‐defibrillator (ICD) therapy and inappropriate ICD interventions were observed in 17%. Presentation with aborted SCD or arrhythmic syncope was the only predictor of adverse outcome in follow‐up (odds ratio: 3.1, 95% confidence interval: 0.7–19.6, p = .001).ConclusionsSymptomatic patients with BrS are more likely to present with spontaneous type 1 Brugada ECG pattern, longer PR interval, and pathogenic mutation in SCN5A gene. Appropriate ICD interventions are more likely in symptomatic patients and those with SCN5A mutation.

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Section: Resultsmentioning

confidence: 66%

Brugada syndrome in Iran: Insights from a 12‐year longitudinal study

Haghjoo,

Askarinejad,

Madadi

et al. 2024

Cardiovasc electrophysiol

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More Severe Loss-of-Function Sodium Channel induced by Compound SCN5A R965C and R1309H Mutants lead to Complex Familial Arrhythmia Syndrome

Lin

Qin

Shen

et al. 2019

Preprint

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Objective: A complex familial arrhythmia syndrome was identified in a Chinese Han family, characterized by sick sinus syndrome, progressive conduction block, atrial fibrillation, atrial standstill and Brugada syndrome. The underlying mechanism associated with the genetic mutation was investigated. Methods: Genetic analysis was conducted for probands in the coding and splicing regions of genes susceptible to cardiac arrhythmia diseases. The stable cell lines overexpressing wild-type (WT) or mutant SCN5A gene were generated in HEK293T cells and electrophysiological recordings were performed to evaluate the functional changes of mutant Na V 1.5 channels. Results: We identified a rare double R965C and R1309H mutations in Na V 1.5 channel, as a heterozygous and compound pattern, locating in the same chromosome.Compared to WT, a single mutation of R965C or R1309H, the compound mutations of R965C-R1309H most dramatically reduced the peak current of Na V 1.5 channel with testing potentials ranging from -35 mV to 25 mV. Notably, the maximal peak current of Na V 1.5 channel carrying R1309H only and R965C-R1309H mutations displayed significant decreases by 31.5% and 73.34%, respectively, compared to WT. Additionally, compared to single mutations of R965C or R1309H, the R965C-R1309H mutations resulted in more obviously depolarization-shifted activation and hyperpolarization-shifted inactivation, also caused most significantly changed time constant, V 1/2 and slope factor of activation and inactivation. Conclusions:The compound mutations of R965C-R1309H led to more dramatically reduced current density of Na v 1.5 channel, as well as more depolarization-shifted activation and hyperpolarization-shifted inactivation than single mutation of R965C or R1309H, which may provide more understanding on the molecular mechanisms underlying the familial arrhythmia syndrome. Author summarySeveral limited types of research about the interaction of compound mutations and the mechanism of interaction remains controversial. Here we report a novel compound mutation R965C-R1309H in SCN5A gene.The compound mutations of R965C-R1309H markedly reduced the Na + current density of Na v 1.5 channel and caused significant depolarization-shifted activation and hyperpolarization-shifted inactivation, suggesting that R965C mutation aggravated the pore gating changes of sodium channel containing R1309H mutation. The R965C located in the S4-like region in the intracellular loop between DII and DIII, and the R1309H located in the S4 helix of DIII as voltage sensor, which thus potentially had synergistic and interacting effects on pore gating properties of the sodium channel. Additionally, the complex familial arrhythmia syndrome simultaneously complicated of early young onset of arrhythmia and harmful prognosis of recurrent ischemic cerebral stroke, even though effective Warfarin anticoagulation. overlap syndrome, heritable/familial arrhythmia syndrome or SCN5A syndrome induced by a single or several SCN5A mutations.Here, we report a Han Chinese family presen...

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Clinical Polymorphisms and Approaches of Arrhythmias Treatment in a Family with p.delKPQ1505-1507 Deletion in SCN5A Gene

Cited by 2 publications

References 33 publications

Brugada syndrome in Iran: Insights from a 12‐year longitudinal study

Brugada syndrome in Iran: Insights from a 12‐year longitudinal study

More Severe Loss-of-Function Sodium Channel induced by Compound SCN5A R965C and R1309H Mutants lead to Complex Familial Arrhythmia Syndrome

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