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Background: Arrhythmogenic cardiomyopathy (ACM) characterized by progressive myocardial loss and replacement with fibro-fatty tissue is a major cause of sudden cardiac death (SCD). In particular, ACM with predominantly left ventricular involvement, known as arrhythmogenic left ventricular cardiomyopathy (ALVC), has a poor prognosis., Methods: The proband underwent whole-exome sequencing (WES) to determine the etiology of ALVC. Family members were then analyzed using PCR and Sanger sequencing. Clinical evaluations including 12-lead ECG, transthoracic echocardiography, and cardiac MRI were performed for all available first-degree relatives., Results: WES identified two variants in the FLNC (c.G3694A) and JUP (c.G1372A) genes, the combination of which results in ALVC and SCD., Conclusion: The present study comprehensively investigates the involvement of two discovered variants of FLNC and JUP in the pathogenesis of ALVC. More study is necessary to elucidate the genetic factors involved in the etiology of ALVC., (© 2024. The Author(s).)

Objective: We studied the clinical and molecular features of a family with hypertrophic cardiomyopathy (HCM)., Background: A very heterogeneous disease affecting the heart muscle, HCM is mostly caused by variants in the proteins of sarcomeres. The detection of HCM pathogenic variants can affect the handling of patients and their families., Methods: Whole-exome sequencing (WES) was performed to assess the genetic cause(s) of HCM in a consanguineous Iranian family., Results: Missense likely pathogenic variant c.1279C>T (p.Arg427Cys) within exon 7 of the LMNA gene (NM_170707) was found. The segregations were confirmed by polymerase chain reaction-based Sanger sequencing., Conclusions: Variant c.1279C>T (p.Arg427Cys) in the LMNA gene seemed to have been the cause of HCM in the family. A few LMNA gene variants related to HCM phenotypes have been recognized so far. Identifying HCM genetic basis confers significant opportunities to understand how the disease can develop and, by extension, how this progression can be arrested. Our study supports WES effectiveness for first-tier variant screening of HCM in a clinical setting., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Health and economies are both affected by the coronavirus disease-19 (COVID-19) global pandemic. Angiotensin-converting enzyme 2 ( ACE2 ) is a polymorphic enzyme that is a part of the renin-angiotensin system, and it plays a crucial role in viral entry. Previous investigations and studies revealed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and ACE2 have a considerable association. Recently, ACE2 variants have been described in human populations in association with cardiovascular and pulmonary conditions. In this study, genetic susceptibility to COVID-19 in different populations was investigated., Methods and Results: We evaluated the identified variants based on the predictive performance of 5 deleteriousness-scoring methods and the 2015 American College of Medical Genetics and Genomics (ACMG) guidelines. The results indicated 299 variants within the ACE2 gene. The variants were analyzed by different in-silico analysis tools to assess their functional effects. Ultimately, 5 more deleterious variants were found in the ACE2 gene., Conclusions: Collecting more information about the variations in binding affinity between SARS-CoV-2 and host-cell receptors due to ACE2 variants leads to progress in treatment strategies for COVID-19. The evidence accumulated in this study showed that ACE2 variants in different populations may be associated with the genetic susceptibility, symptoms, and outcome of SARS-CoV-2 infection., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Taravat Talebi et al.)

Background: Long QT syndrome (LQTS) is a lethal cardiac condition. However, the clinical implementation of genetic testing has now made LQTS eminently treatable. Next-generation sequencing has remarkable potential for both clinical diagnostics and research of LQTS. Here, we investigated the genetic etiology in an LQTS-suspected Iranian pedigree by whole-exome sequencing and collected all KCNH2 variants with consensus based on publications., Methods: WES was performed on the proband of this pedigree to reveal the underlying cause of sudden cardiac death (SCD). The variant found was validated and segregated by polymerase chain reaction and Sanger sequencing. Based on the literature review, KCNH2 variants were retrospectively analyzed to identify pathogenic variants, likely pathogenic variants, and variants of uncertain significance by using different prediction tools., Results: WES identified an autosomal dominant nonsense variant, c.1425C>A: p.Tyr475Ter, in the KCNH2 gene, which appeared to be the most likely cause of LQTS in this pedigree. Moreover, our comprehensive literature review yielded 511 KCNH2 variants in association with the LQTS phenotype, with c.3002G>A (CADD Phred=49) being the most pathogenic variant., Conclusions: Variants in the KCNH2 gene are considered a major cause of LQTS worldwide. The detected c.1425C>A is a novel variant to be reported from Iran for the first time. This result indicates the importance of KCNH2 screening in a pedigree with SCD cases., Competing Interests: The authors declare that they have no competing interests., (© 2023 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

Background: Alexander disease (AxD) is a rare leukodystrophy with an autosomal dominant inheritance mode. Variants in GFAP lead to this disorder and it is classified into three distinguishable subgroups: infantile, juvenile, and adult-onset types., Objective: The aim of this study is to report a novel variant causing AxD and collect all the associated variants with juvenile and adult-onset as well., Methods: We report a 2-year-old female with infantile AxD. All relevant clinical and genetic data were evaluated. Search strategy for all AxD types was performed on PubMed. The extracted data include total recruited patients, number of patients carrying a GFAP variant, nucleotide and protein change, zygosity and all the clinical symptoms., Results: A novel de novo variant c.217A > G: p. Met73Val was found in our case by whole-exome sequencing. In silico analysis categorized this variant as pathogenic. Totally 377 patients clinically diagnosed with juvenile or adult-onset forms were recruited in these articles, among them 212 patients were affected with juvenile or adult-onset form carrier of an alteration in GFAP. A total of 98 variants were collected. Among these variants c.262C > T 11/212 (5.18%), c.1246C > T 9/212 (4.24%), c.827G > T 8/212 (3.77%), c.232G > A 6/212 (2.83%) account for the majority of reported variants., Conclusion: This study highlighted the role of genetic in AxD diagnosing. It also helps to provide more information in order to expand the genetic spectrum of Iranian patients with AxD. Our literature review is beneficial in defining a better genotype-phenotype correlation of AxD disorder., (© 2022. The Author(s).)

Objective: Children with a specific learning disability (SLD) have deficits in social and academic competence and executive function (EF). In this study, we used the Model of Human Occupation to investigate the effect of peer-play activities on occupational values and competence as well as EF skills (i.e., behavior regulation and metacognition) in children with SLD., Method: Forty-nine children ages 7-11 yr with SLD were randomly assigned to the peer-play and control groups. Outcome measures were the Behavior Rating Inventory of Executive Function and the Child Occupational Self-Assessment (COSA)., Results: Data analysis showed that the effects of the intervention on EF skills were medium to large. The occupational values and competence did not change according to the COSA., Conclusion: Occupational therapy practitioners can use peer-play activities to enhance EF in children with SLD; however, perceived occupational values and competence may not show any changes with the peer-play intervention using a self-assessment instrument., (Copyright © 2019 by the American Occupational Therapy Association, Inc.)

Background: A marked stress response including hypertension, tachycardia, arrhythmias and an increase in intracranial pressure often follows direct laryngoscopy. This response can be harmful specially in patients with underlying cardiac disease. The intubating laryngeal mask airway (ILMA)--a new modified laryngeal mask airway--has been introduced that facilitates tracheal intubation without using laryngoscopy. Oropharyngeal stimulation-proposed as the probable cause of stress response--have been shown to be attenuated in ILMA. We conducted this study to evaluate the stress response following two techniques in patients undergoing coronary artery surgery which are most likely to benefit from decreased hemodynamic changes during intubation., Methods: In this trial, eighty patients, forty in ILMA group and forty in DL group were involved. To determine hemodynamic response during these manipulations, blood pressure (BP) and heart rate (HR) were recorded before and after anesthetic induction (one minute before and one, two and five minutes after successful intubation via either method)., Results: A significant increase in heart rate and blood pressure was detected in both groups after intubation. Despite existence of noted changes in both groups; quantity of these changes was similar in both groups, however quality of changes was not completely similar., Conclusion: Finally we could hardly ascertain if intubation with ILMA is a prefered method in patients with high cardiac risk or not. But it seems that ILMA does not have much greater benefit over conventional DL in patients undergoing coronary artery by-pass grafting.