Publications by authors named "Majid Maleki"

96 Publications

Innovations in cardiovascular imaging.

Trends Cardiovasc Med 2021 Feb 3. Epub 2021 Feb 3.

Professor of Cardiology, Interventional Cardiologist Echocardiologist, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.

Cardiovascular diseases are culpable for the majority of mortalities the world over, hence the significance of advances in preventive medicine and imaging. Cardiovascular imaging constitutes the cornerstone of not only early but also precise diagnoses. Indeed, advanced imaging enables cardiologists to make efficacious management plans for various heart conditions. The present article discusses essential innovations in cardiovascular imaging.
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http://dx.doi.org/10.1016/j.tcm.2021.01.007DOI Listing
February 2021

Deep COVID DeteCT: an international experience on COVID-19 lung detection and prognosis using chest CT.

NPJ Digit Med 2021 Jan 29;4(1):11. Epub 2021 Jan 29.

Department of Radiology, School of Medicine, Stanford University, Stanford, CA, 94305, USA.

The Coronavirus disease 2019 (COVID-19) presents open questions in how we clinically diagnose and assess disease course. Recently, chest computed tomography (CT) has shown utility for COVID-19 diagnosis. In this study, we developed Deep COVID DeteCT (DCD), a deep learning convolutional neural network (CNN) that uses the entire chest CT volume to automatically predict COVID-19 (COVID+) from non-COVID-19 (COVID-) pneumonia and normal controls. We discuss training strategies and differences in performance across 13 international institutions and 8 countries. The inclusion of non-China sites in training significantly improved classification performance with area under the curve (AUCs) and accuracies above 0.8 on most test sites. Furthermore, using available follow-up scans, we investigate methods to track patient disease course and predict prognosis.
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http://dx.doi.org/10.1038/s41746-020-00369-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846563PMC
January 2021

Effects of intravenous and transdermal photobiomodulation on the postoperative complications of coronary artery bypass grafting surgery: a randomized, controlled clinical trial.

Lasers Med Sci 2021 Jan 4. Epub 2021 Jan 4.

Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.

Although coronary artery bypass graft (CABG) surgery is one of the most worldwide commonly performed cardiac surgeries to enhance myocardial perfusion in high-grade myocardial occlusion, it remains a high-risk procedure. Photobiomodulation (PBM) is one of the methods which have been shown to have positive effects on the healing process after CABG and postoperative complications. The aim of this study was to evaluate the efficacy of PBM in patients who underwent a coronary artery bypass graft (CABG). Ths study was conducted with 192 volunteers who electively submitted to CABG. The volunteers were randomly allocated into two groups: laser-treated (transdermal: 980 nm, 200 mW, continuous, average energy fluency of 6 J/cm and intravenous: 405 nm, 1.5 mW, continuous for 30 min) and standard treatment and control group (standard treatment only). Intravenous laser was illuminated the day before the surgery, immediately after transferring the patient to CCU post-operation and IV laser in addition to transdermal laser was applied every day after surgery for 6 days. A total of 170 out of 192 participants completed the study, 82 (48.2%) in the PBM group and 88 (51.8%) in the control group. Level of LDH and CPK was significantly lower in the PBM group (P < 0.05) in the 4th day postoperatively. The PBM group also showed significantly lower post-surgery complications, including pericardial effusion, ejection fraction, pathologic ST changes, pathologic Q, rehospitalization, heart failure, and mediastinitis (P < 0.05). Likewise, the VAS pain score after surgery was significantly lower in patients in the laser group (P < 0.05). PBM seems a promising, safe, cost-benefit therapeutic modality to reduce postoperative complications of CABG. Trial registration number: IRCT2016052926069N4 .
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http://dx.doi.org/10.1007/s10103-020-03236-3DOI Listing
January 2021

MicroRNAs: roles in cardiovascular development and disease.

Cardiovasc Pathol 2021 Jan - Feb;50:107296. Epub 2020 Oct 3.

Department of Botany, University of Rajasthan, Jaipur, Rajasthan, India. Electronic address:

Cardiovascular diseases (CVDs) comprise a group of disorders ranging from peripheral artery, coronary artery, cardiac valve, cardiac muscle, and congenital heart diseases to arrhythmias and ultimately, heart failure. For all the advances in therapeutics, CVDs are still the leading cause of mortality the world over, hence the significance of a thorough understanding of CVDs at the molecular level. Disparities in the expressions of genes and microRNAs (miRNAs) play a crucial role in the determination of the fate of cellular pathways, which ultimately affect an organism's physiology. Indeed, miRNAs serve as the regulators of gene expressions in that they perform key functions both in several important cellular pathways and in the regulation of the onset of various diseases such as CVDs. Many miRNAs are expressed in embryonic, postnatal, and adult hearts; their aberrant expression or genetic deletion is associated with abnormal cardiac cell differentiation, disruption in heart development, and cardiac dysfunction. A substantial body of evidence implicates miRNAs in CVD development and suggests them as diagnostic biomarkers and intriguing therapeutic tools. The present review provides an overview of the history, biogenesis, and processing of miRNAs, as well as their function in the development, remodeling, and diseases of the heart.
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http://dx.doi.org/10.1016/j.carpath.2020.107296DOI Listing
December 2020

Intermediate versus standard-dose prophylactic anticoagulation and statin therapy versus placebo in critically-ill patients with COVID-19: Rationale and design of the INSPIRATION/INSPIRATION-S studies.

Thromb Res 2020 12 24;196:382-394. Epub 2020 Sep 24.

Cardiovascular Intervention Research Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Iran; Clinical Trial Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Iran. Electronic address:

Background: Microvascular and macrovascular thrombotic events are among the hallmarks of coronavirus disease 2019 (COVID-19). Furthermore, the exuberant immune response is considered an important driver of pulmonary and extrapulmonary manifestations of COVID-19. The optimal management strategy to prevent thrombosis in critically-ill patients with COVID-19 remains unknown.

Methods: The Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) and INSPIRATION-statin (INSPIRATION-S) studies test two independent hypotheses within a randomized controlled trial with 2 × 2 factorial design. Hospitalized critically-ill patients with reverse transcription polymerase chain reaction confirmed COVID-19 will be randomized to intermediate-dose versus standard dose prophylactic anticoagulation. The 600 patients undergoing this randomization will be screened and if meeting the eligibility criteria, will undergo an additional double-blind stratified randomization to atorvastatin 20 mg daily versus matching placebo. The primary endpoint, for both hypotheses will be tested for superiority and includes a composite of adjudicated acute arterial thrombosis, venous thromboembolism (VTE), use of extracorporeal membrane oxygenation, or all-cause death within 30 days from enrollment. Key secondary endpoints include all-cause mortality, adjudicated VTE, and ventilator-free days. Key safety endpoints include major bleeding according to the Bleeding Academic Research Consortium definition and severe thrombocytopenia (platelet count <20,000/fL) for the anticoagulation hypothesis. In a prespecified secondary analysis for non-inferiority, the study will test for the non-inferiority of intermediate intensity versus standard dose anticoagulation for major bleeding, considering a non-inferiority margin of 1.8 based on odds ratio. Key safety endpoints for the statin hypothesis include rise in liver enzymes >3 times upper normal limit and clinically-diagnosed myopathy. The primary analyses will be performed in the modified intention-to-treat population. Results will be tested in exploratory analyses across key subgroups and in the intention-to-treat and per-protocol cohorts.

Conclusions: INSPIRATION and INSPIRATON-S studies will help address clinically-relevant questions for antithrombotic therapy and thromboinflammatory therapy in critically-ill patients with COVID-19.
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http://dx.doi.org/10.1016/j.thromres.2020.09.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7513771PMC
December 2020

Insights into role of microRNAs in cardiac development, cardiac diseases, and developing novel therapies.

Iran J Basic Med Sci 2020 Aug;23(8):961-969

Cardiogenetic Research Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, Iran.

MicroRNAs (miRNAs) are a subfamily of small noncoding RNAs that play a variety of roles in regulating gene expression in nearly all organisms. They affect different biological pathways by post-transcriptionally regulating mRNAs. Aside from miRNAs' role in maintaining cellular homeostasis, their perturbation is related to several pathologic states and diseases. Cardiovascular disorders are considered some of the most mortal multifactorial diseases that are caused by the deregulation of network of genes and effects of environmental factors. In this review, we discuss the role of miRNAs in cardiac homeostasis and malfunctions. We reviewed published research on association and role of miRNAs in cardiac development and diseases and investigated the possible links between regulatory miRNAs and different cardiac disorders. Research shows that manipulating miRNAs expression affects the integrity and functionality of the cardiovascular system. Moreover, deregulation of miRNAs, is observed in many cardiac diseases. These findings intensify the pivotal role of miRNAs in the development and specific pathological disorders of the cardiovascular system. In this review, we summarized the latest findings on the involvement of miRNAs in cardiac development, and continued by their role in congenital heart diseases and rheumatic heart disease, which are some of the leading causes of infant death and cardiovascular morbidity and mortality. Considering the significance of miRNAs in cardiac homeostasis and malfunctions, they are considered as promising therapeutic targets in cardiovascular diseases.
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http://dx.doi.org/10.22038/ijbms.2020.40974.10015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478248PMC
August 2020

Preparation, escalation, de-escalation, and normal activities.

J Card Surg 2020 Sep 16. Epub 2020 Sep 16.

Cardio-Oncology Research Center, Rajaie Cardiovascular, Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.

Iran is one of the earliest countries involved with coronavirus disease 2019 (COVID-19) pandemic. In the present short report, we have presented our experiences as a cardiovascular tertiary center during the COVID-19 outbreak. At the beginning, we have pursued our activities in four field of administrative, preventative, therapeutic, and research. Then by gaining new experiences, we have tailored our strategies. Finally, we have described our challenges and future strategies on returning to normal activities.
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http://dx.doi.org/10.1111/jocs.15033DOI Listing
September 2020

Prevention of anthracycline-induced cardiotoxicity: a systematic review and network meta-analysis.

Int J Clin Pharm 2021 Feb 10;43(1):25-34. Epub 2020 Sep 10.

Department of Biostatistics, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background Anthracycline based chemotherapy is commonly used in many malignancies. While life expectancy increases with the use of this medication, cardiac toxicity causes a risk for patients' health due to anthracyclines. Objective This systematic review and meta-analysis emphasizes on prevention of anthracycline-associated cardiotoxicity in breast cancer and lymphoma patients. Methods We conducted a systematic review of electronic databases including PubMed, Medline, EMBASE, ClinicalTrials.gov, Web of Science, and the Cochrane Library from inception to June 2019 collecting published articles on primary prevention of anthracycline-associated cardiotoxicity in breast cancer and lymphoma patients. We conducted a network meta-analysis and a pairwise meta-analysis in order to compare direct and indirect cardiac agents group with control group calculate left ventricular ejection fraction change. Primary studies results were pooled using random effects model, frequent network meta-analyses, and performed pairwise meta-analysis using netmeta and meta packages respectively in R software version 3.5.1. Results Twelve studies reported left ventricular ejection fraction outcome among 526 patients in the cardiac agent group and 508 in the control group. Based on Surface Under the Cumulative Ranking cure result, spironolactone was the best in left ventricular ejection fraction change and based on meta-analysis, cardiac group had 1.98 unit left ventricular ejection fraction more than the control group (MD = 1.98, 95% CI 0.15-3.81, p value = 0.03). Conclusions The amount of left ventricular ejection fraction used by cardiac agents in anthracycline-based chemotherapy was reduced to a lesser extent. The effective and ineffective drugs were spironolactone and metoprolol, respectively.
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http://dx.doi.org/10.1007/s11096-020-01146-6DOI Listing
February 2021

Coarctation Stenting in a Rare Case with Congenitally Corrected Transposition of the Great Arteries and the Bicuspid Aortic Valve.

J Tehran Heart Cent 2020 Jan;15(1):27-30

Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran.

Congenitally corrected transposition of the great arteries (cc-TGA) is a rare congenital abnormality that occurs in 1 per 33000 live births. This abnormality comprises nearly 0.05% of all congenital heart defects, with at least 90% of cc-TGA patients having associated cardiac defects; some of these associated defects are, however, very rare. In this case report, we describe a 22-year-old man who referred to our hospital for the evaluation of hypertension and cardiac murmurs. Via echocardiography and catheterization, the patient was finally diagnosed with cc-TGA, bicuspid aortic valve, and coarctation of the aorta. He underwent successful percutaneous transarterial coarctoplasty without any complications at early and 6 months' follow-up visits.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360863PMC
January 2020

Pocket-sized echocardiography for screening structural heart disease: diagnostic accuracy and cost-effectiveness for population-based studies.

Cardiol Young 2020 Feb 9;30(2):197-204. Epub 2020 Jan 9.

Heart Valve Disease Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.

Background: The standard transthoracic echocardiography has some limitations in emergent and community-based situations. The emergence of pocket-sized ultrasound has led to influential advancements.

Methods: In this prospective study, in the hospital-based phase, children with suspected structural heart diseases were enrolled. In the school-based phase, healthy children were randomly selected from six schools. All individuals were examined by experienced operators using both the standard and the pocket-sized echocardiography.

Results: A total of 73 individuals with a mean age of 9.9 ± 3.2 years in the hospital-based cohort and 143 individuals with a mean age of 12.8 ± 2.9 years in the school-based cohort were examined. The agreements between the standard and the pocket-sized echocardiography were good or excellent for major CHDs in both cohorts (κ statistics > 0.61). Among valvular pathologies, agreements for tricuspid and pulmonary valves' regurgitation were moderate among school-based cohorts (0.56 [95% confidence interval 0.12-1] and 0.6 [95% confidence interval 0.28-0.91], respectively). The agreements for tricuspid and pulmonary valves' regurgitation were excellent (>0.9) among hospital-based population. Other values for valvular findings were good or excellent. The overall sensitivity and specificity were 87.5% (95% confidence interval 47.3-99.7) and 93.8% (95% confidence interval 85-98.3) among the hospital-based individuals, respectively, and those were 88% (95% confidence interval 77.8-94.7) and 68.4% (95% confidence interval 56.7-78.6) among the school-based individuals, respectively. The cost of examination was reduced by approximately 70% for an individual using the pocket-sized device.

Conclusions: When interpreted by experienced operators, the pocket-sized echocardiography can be used as screening tool among school-aged population.
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http://dx.doi.org/10.1017/S1047951119003111DOI Listing
February 2020

Cardio-oncology discipline: focus on the necessities in developing countries.

ESC Heart Fail 2020 10 30;7(5):2175-2183. Epub 2020 Jun 30.

Echocardiography Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.

Cardiovascular diseases constitute one of the main aetiologies of mortality among patients with cancer. Population ageing and cancer survival rate improvements have resulted in the coexistence of cardiovascular diseases and malignancies in an increasing number of patients. With the diversity in treatments and the introduction of new drug lines, multiple mechanisms of cardiovascular injury have been recognized in these patients. Cardio-oncology is an emerging entity introduced to provide a proper solution to the several challenges encountered in the management of patients with cancer and cardiac involvement. This review will assess the logical grounds for establishing a cardio-oncology unit, describe the main objectives and the detailed responsibilities in such systems, and outline the target population. Furthermore, the importance of research and appropriate data collection will be highlighted. Lastly, the special considerations and modifications required for setting up such centres in the developing countries are discussed.
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http://dx.doi.org/10.1002/ehf2.12838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524122PMC
October 2020

Effects of the COVID-19 Pandemic on the Management of Patients With ST-elevation Myocardial Infarction in a Tertiary Cardiovascular Center.

Crit Pathw Cardiol 2021 03;20(1):53-55

From the Cardiovascular Intervention Research Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, Iran; and.

Background: In the Coronavirus Disease 2019 (COVID-19) pandemic, the appropriate reperfusion strategy in patients with ST-segment elevation myocardial infarction (STEMI) is unclear.

Methods: This retrospective single-center study consecutively enrolled patients who presented with STEMI and scheduled for primary percutaneous coronary intervention (PPCI) during the outbreak of COVID-19. Due to the delay in the reporting of the polymerase chain reaction test results, our postprocedural triage regarding COVID-19, followed by the isolation strategy, was based on lung computerized tomography scan results.

Results: Forty-eight patients with STEMI referred to our center. PPCI was done for 44 (91%) of these patients. The mean symptom-to-device time was 490.93 ± 454.608 minutes, and the mean first medical contact-to-device time was and 154.12 ± 36.27 minutes. Nine (18%) patients with STEMI were diagnosed as having typical/indeterminate features indicating COVID-19 involvement. During hospitalization, 1 (2.0%) patient died of cardiogenic shock. The study population was followed for 35.9 ± 12.7 days. Two patients expired in another centers due to COVID-19. No cardiac catheterization laboratory staff members were infected by COVID-19 during the study period.

Conclusions: Our small report indicates that by taking the recommended safety measures and using appropriate PPE, we can continue PPCI as the main reperfusion strategy safely and effectively.
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http://dx.doi.org/10.1097/HPC.0000000000000228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288762PMC
March 2021

Presence and prognostic value of ventricular diastolic function in arrhythmogenic right ventricular cardiomyopathy.

Echocardiography 2020 11 27;37(11):1766-1773. Epub 2020 May 27.

Echocardiography Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.

Introduction: Limited data exist regarding the presence and importance of diastolic parameters in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). We sought to evaluate RV diastolic parameters and echo-based diastolic predictors of major adverse cardiovascular events (MACE).

Method: 48 patients with a definitive diagnosis of ARVC were included and followed for 6-18 months. A comprehensive standard two-dimensional (2D) transthoracic echocardiography (TTE) with precise evaluation of systolic and diastolic indices of both ventricles was done. RV isovolumetric relaxation time (IVRT), RV myocardial performance index (MPI), and right atrial (RA) volume were evaluated.

Results: 48 patients (mean age = 38.5 ± 14 years; 79.2% male) were enrolled. 27.3% had grade I, 68.2% had grade II, and 4.5% had grade III RV diastolic dysfunction. In 12-month follow-up, 12 patients (25%, with mean RV3DEF = 24.8 ± 9%) experienced MACE and required hospitalization: ventricular tachyarrhythmia in 7 patients (14.6%), RV clot in 2 subjects (4.2%), and right-sided failure in 3 cases (6.3%). In logistic regression analysis, tissue Doppler velocity of tricuspid annulus (e' TV) (P = .02, OR = 0.581, CI = 0.368-0.917), peak E mitral valve (P = .043, OR = 0.95, CI = 0.913-0.999), tissue Doppler velocity of septal e' (P = .052, OR = 0.733, CI = 0.536-1.003), and MPI (P = .009, OR = 95, CI = 3.083-2942) were powerful predictors of MACE.

Conclusion: In our study, RV diastolic function parameters including e' TV and e' MV, RA volume and area, and RV MPI were powerful predictors of MACE and may be considered during the baseline and follow-up of the ARVC patients.
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http://dx.doi.org/10.1111/echo.14716DOI Listing
November 2020

Rivaroxaban in patients undergoing surgical mitral valve repair.

J Thromb Thrombolysis 2020 Apr;49(3):475-479

Heart Valve Diseases Research Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Vali-Asr Ave, 1995614331, Tehran, Iran.

In patients undergoing mitral valve repair (MVre), a 3-month course of anticoagulation is currently recommended. The role of the non-vitamin K antagonist oral anticoagulants has here been scarcely studied. In the present mixed cohort study, the safety and efficacy of rivaroxaban (prospective analysis) were compared with those of warfarin (retrospective analysis) in patients undergoing MVre. Anticoagulation therapy was continued for at least 3 months, and the patients were followed for 1 year following surgery. The present study recruited 736 patients undergoing MVre with or without concomitant coronary artery bypass or surgical repair on the other valves. Concomitant valvular replacement and severe chronic kidney diseases were the most important exclusion criteria. The final analysis was conducted on 153 patients treated with rivaroxaban and 144 patients treated with warfarin. Dissimilarities in baseline characteristics necessitated propensity score matching, in which 104 patients in each group were compared. No major bleeding or cerebrovascular accident occurred during the 1-year follow-up. Clinically relevant non-major bleeding was reported in 2 patients in the rivaroxaban group and 4 patients in the warfarin group, a difference non-statistically significant before and after propensity score matching (P = 0.371 and P = 0.407, respectively). The type of anticoagulation did not predict the 1-year outcome (HR 2.165, 95% CI 0.376 to 12.460; P = 0.387). In this mixed cohort study, rivaroxaban was both safe and efficient in patients with MVre. Such preliminary results should prompt larger randomized controlled trials.
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http://dx.doi.org/10.1007/s11239-020-02046-2DOI Listing
April 2020

Small Molecules with Big Impacts on Cardiovascular Diseases.

Biochem Genet 2020 Jun 29;58(3):359-383. Epub 2020 Jan 29.

Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.

Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide. Although in recent years there has been a significant progress in the diagnosis, treatment, and prognosis of CVD, but due to their complex pathobiology, developing novel biomarkers and therapeutic interventions are still in need. MicroRNAs (miRNAs) are a fraction of non-coding RNAs that act as micro-regulators of gene expression. Mounting evidences over the last decade confirmed that microRNAs were deregulated in several CVDs and manipulating their expression could affect homeostasis, differentiation, and function of cardiovascular system. Here, we review the current knowledge concerning the roles of miRNAs in cardiovascular diseases with more details on cardiac remodeling, arrhythmias, and atherosclerosis. In addition, we discuss the latest findings on the potential therapeutic applications of miRNAs in cardiovascular diseases.
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http://dx.doi.org/10.1007/s10528-020-09948-zDOI Listing
June 2020

A novel de novo dominant mutation of NOTCH1 gene in an Iranian family with non-syndromic congenital heart disease.

J Clin Lab Anal 2020 Apr 22;34(4):e23147. Epub 2019 Dec 22.

Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.

Background: Congenital heart disease (CHD) is the most common birth defect which can arises from different genetic defects. The genetic heterogeneity of this disease leads to restricted success in candidate genes screening method. Emerging approaches such as next-generation sequencing (NGS)-based genetic analysis might provide a better understating of CHD etiology in the patients who are left undiagnosed. To this aim, in this study, we survived the causes of CHD in an Iranian family who was consanguineous and had two affected children.

Methods: Affected individuals of this family were checked previously by PCR-direct sequencing for six candidate genes (NKX2-5, ZIC3, NODAL, FOXH1, GJA1, GATA4) and had not revealed any reported CHD causative mutations. Whole-exome sequencing (WES) was performed on this family probond to determine the underlying cause of CHD, and the identified variants were confirmed and segregated by Sanger sequencing.

Results: We identified one heterozygous missense mutation, c.T6797C (p.Phe2266Ser), in the NOTCH1 gene, which seems to be the most probably disease causing of this family patients. This mutation was found to be novel and not reported on 1000 Genomes Project, dbSNP, and ExAC.

Conclusion: Worldwide, mutations in NOTCH1 gene are considered as one of the most known causes of CHD. The found NOTCH1 variant in this family affected individuals was the first report from Iran. Yet again, this result indicates the importance of NOTCH1 screening in CHD patients.
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http://dx.doi.org/10.1002/jcla.23147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171333PMC
April 2020

Modulatory Role of SIRT1 and Resistin as Therapeutic Targets in Patients with Aortic Valve Stenosis.

Arch Med Res 2019 08 31;50(6):333-341. Epub 2019 Oct 31.

Rajaie Cardiovascular, Medical, and Research Centre, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Inflammatory is one of the main cause of aortic valve stenosis (AS), so discovering novel biomarkers for the targeted therapy of inflammation could be an attractive strategy in AS prevention. The objectives of our study were to clarify the modulatory role of resistin and silent information regulator 1 (SIRT1) before and after surgery and also to evaluate the therapeutic effects of resveratrol.

Methods: Nineteen AS patients and 15 healthy subjects were studied as the case and control groups, respectively. Peripheral blood mononuclear cells (PBMCs) were isolated and cultured to determine the levels of resistin and SIRT1 and the effects of resveratrol on them.

Results: Significant increase in resistin expression was observed in the patients compare to the control (p ≤0.01), and this upregulation was augmented 72 h following surgery (p ≤0.01). The SIRT1 expression decreased in the AS group compare to the control but this reduction was not significant. Aortic valve replacement caused a higher decrease in the protein (p ≤0.01) and mRNA level (p ≤0.05) of SIRT1. Resveratrol in the AS group significantly diminished the resistin level (p ≤0.05) but increased the SIRT1 level (p ≤0.001).

Conclusions: In our patients with AS, the resistin level was increased, whereas the expression of SIRT1 was reduced and surgery augmented these alterations. Resveratrol improved inflammation in the PBMCs of the patients through the SIRT1/resistin pathway. These findings suggest that pharmacological therapy with resveratrol might be a novel approach to alleviating inflammation in patients with AS.
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http://dx.doi.org/10.1016/j.arcmed.2019.10.001DOI Listing
August 2019

MFP-Unet: A novel deep learning based approach for left ventricle segmentation in echocardiography.

Phys Med 2019 Nov 28;67:58-69. Epub 2019 Oct 28.

Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.

Segmentation of the Left ventricle (LV) is a crucial step for quantitative measurements such as area, volume, and ejection fraction. However, the automatic LV segmentation in 2D echocardiographic images is a challenging task due to ill-defined borders, and operator dependence issues (insufficient reproducibility). U-net, which is a well-known architecture in medical image segmentation, addressed this problem through an encoder-decoder path. Despite outstanding overall performance, U-net ignores the contribution of all semantic strengths in the segmentation procedure. In the present study, we have proposed a novel architecture to tackle this drawback. Feature maps in all levels of the decoder path of U-net are concatenated, their depths are equalized, and up-sampled to a fixed dimension. This stack of feature maps would be the input of the semantic segmentation layer. The performance of the proposed model was evaluated using two sets of echocardiographic images: one public dataset and one prepared dataset. The proposed network yielded significantly improved results when comparing with results from U-net, dilated U-net, Unet++, ACNN, SHG, and deeplabv3. An average Dice Metric (DM) of 0.953, Hausdorff Distance (HD) of 3.49, and Mean Absolute Distance (MAD) of 1.12 are achieved in the public dataset. The correlation graph, bland-altman analysis, and box plot showed a great agreement between automatic and manually calculated volume, area, and length.
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http://dx.doi.org/10.1016/j.ejmp.2019.10.001DOI Listing
November 2019

Q Fever Endocarditis in Iran.

Sci Rep 2019 10 24;9(1):15276. Epub 2019 Oct 24.

National Reference Laboratory for Plague, Tularemia and Q fever, Research Centre for Emerging and Reemerging Infectious Diseases, Pasteur Institute of Iran, Akanlu, Kabudar Ahang, Iran.

Patients with the underlying valvular heart disease are at the high risk of developing sub-acute or chronic endocarditis secondary to Coxiella burnetii. Q fever endocarditis is the most common manifestation along with persistent the infection. There is some serologic and molecular evidence of C. burnetii infection in humans and livestock in Iran. As it is possible to observe chronic Q fever in Iran, it seems necessary to study the prevalence of Q fever endocarditis in this country. In the present study, Infective Endocarditis (IE) patients (possible or definite based on Duke Criteria) hospitalized in Rajaie Cardiovascular Medical and Research Center were enrolled from August 2016 to September 2018. Culture-negative endocarditis patients were evaluated by Raoult criteria for diagnosis Q fever endocarditis. The serological results for brucellosis were negative for all subjects. All blood and tissue samples including valve samples were tested for C. burnetii infection using serology and Polymerase Chain Reaction (PCR). In this study, 126 patients who were admitted to the hospital were enrolled; of which 52 subjects were culture-negative IE. Among the participants, 16 patients (30.77%) were diagnosed with Q fever IE and underwent medical treatment. The mean age of patients was 46.6 years ranging from 23 to 69 years and 75% of them were male. Considering the high prevalence of Q fever IE, evaluation of the patients with culture-negative IE for C. burnetii infections was highly recommended.
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http://dx.doi.org/10.1038/s41598-019-51600-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6813299PMC
October 2019

GATA4 screening in Iranian patients of various ethnicities affected with congenital heart disease: Co-occurrence of a novel de novo translocation (5;7) and a likely pathogenic heterozygous GATA4 mutation in a family with autosomal dominant congenital heart disease.

J Clin Lab Anal 2019 Sep 22;33(7):e22923. Epub 2019 May 22.

Cardiogenetics Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.

Background: Congenital heart disease (CHD) is the most common birth defect and a major health problem around the world. However, its exact etiology has remained unclear. Among various genetic contributing factors, GATA4 transcription factor plays a significant role in the CHD pathogenesis. In this study, GATA4 coding sequence was screened in Iranian patients of various ethnicities.

Methods: Sixty six individuals with familial CHD referred to our center were recruited in this study. After receiving written informed consent from each individual or their parents, chromosomal analyses and GATA4 variant screening were performed. Pathogenicity of the suspected variants was evaluated using available online software tools: CADD, Mutation Taster, SIFT, and PolyPhen-2.

Results: A total of twelve GATA4 variants were detected including five intronic, 2 exonic and 3 polymorphisms as well as 2 missense mutations, the c.1220C>A and c.1309G>A. Unlike the c.1220C>A, the likely pathogenic heterozygous c.1309G>A has not been previously associated with any phenotype. Here, we not only report, for the first time, a c.1309G>A-related CHD, but also report a novel de novo balanced translocation, 46,XY,t(5;7)(qter13;qter11), in the same patient which may have influenced the disease severity.

Conclusion: From screening GATA4 sequence in 66 Iranian patients of various ethnicities, we conclude that cytogenetic analysis and PCR-direct sequencing of different candidate genes may not be the best approach for genetic diagnosis in CHD. Applying novel approaches such as next-generation sequencing (NGS) may provide a better understating of genetic contributing factors in CHD patients for whom conventional methods could not reveal any genetic causative factor.
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http://dx.doi.org/10.1002/jcla.22923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6757118PMC
September 2019

Short-Duration High-Intensity Interval Exercise Training Is More Effective Than Long Duration for Blood Pressure and Arterial Stiffness But Not for Inflammatory Markers and Lipid Profiles in Patients With Stage 1 Hypertension.

J Cardiopulm Rehabil Prev 2019 01;39(1):50-55

Department of Biological Sciences in Sport and Health, Faculty of Sports Sciences and Health, Shahid Beheshti University, Tehran, Iran (Drs Aghaei Bahmanbeglou, Ebrahim, and Ahmadizad); and Cardiovascular Intervention Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran (Drs Maleki and Nikpajouh).

Purpose: The present study compared the effects of 2 different high-intensity interval training (HIIT) protocols on arterial stiffness, lipid profiles, and inflammatory markers in hypertensive patients.

Methods: Thirty hypertensive (stage 1) patients, aged 48.0 ± 3.2 yr, were randomly allocated to the short-duration HIIT (SDHIIT, n = 10), long-duration HIIT (LDHIIT, n = 10), and control (n = 10) groups. After a 2-wk preparatory phase of continuous mild training, patients in the SDHIIT group performed 8 wk of HIIT including 27 repetitions of 30-sec activity at 80% to 100% of (Equation is included in full-text article.)O2peak interspersed with 30-sec passive/active (10%-20% of (Equation is included in full-text article.)O2peak) recovery. Patients in the LDHIIT group performed 8 wk of HIIT, 32 min/session including 4 repetitions of 4-min activity at 75% to 90% of (Equation is included in full-text article.)O2peak interspersed with 4-min passive/active (15%-30% of (Equation is included in full-text article.)O2peak) recovery. Blood pressure (BP), pulse wave velocity (PWV), inflammatory markers, and lipid profiles were measured before and after training.

Results: Significant (P < .05) reductions in systolic blood pressure and PWV were found following 2 training protocols, though, only the changes in PWV following the SDHIIT were significantly different than those in the LDHIIT and control groups. Interleukin-6 and triglycerides decreased and interleukin-10 increased significantly (P < .01) following both HIIT programs, whereas the differences between the 2 training protocols were not statistically significant. C-reactive protein and lipids did not change significantly following HIIT.

Conclusions: Performing HIIT improves systolic blood pressure and inflammatory markers in patients with stage 1 hypertension irrespective of the HIIT intensity and duration, and PWV improvement is intensity related.
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http://dx.doi.org/10.1097/HCR.0000000000000377DOI Listing
January 2019

Mosaic trisomy 22 in a 4-year-old boy with congenital heart disease and general hypotrophy: A case report.

J Clin Lab Anal 2019 Feb 26;33(2):e22663. Epub 2018 Sep 26.

Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.

Background: Trisomy 22 mosaicism is a rare autosomal anomaly with survival compatibility. Recognition of the complete trisomy 22 which is incompatible with life from the mosaic form is critical for genetic counseling. Affected mosaic cases have prevalent clinical presentations such as webbed neck, developmental delay, abnormal ears, cardiac disorders, and microcephaly. Phenotype of these patients is milder than full chromosomal aneuploidy, and the severity of the phenotype depends on the count of trisomic cells. We describe a 4-year-old boy with mosaic trisomy 22 from healthy parents and no family history of any genetic disorders in the pedigree.

Method And Results: The patient had determined dysmorphic clinical features including facial asymmetry, cleft palate, gastroenteritis, hydronephrosis, developmental delay, genital anomalies, dysplastic toenails, flattened nasal bridge, congenital heart defect, hearing loss, cryptorchidism, and hypotonic muscle. He is the first reported with hypothyroidism and larynx wall thickness in worldwide and the first with atrial septal defect (ASD) from Iran. Chromosomal analyses using G-banding indicated a de novo Mos 47,XY,+22(6)/46,XY(44) karyotype with no other chromosomal structural changes.

Conclusions: Our observations confirm the importance of cytogenetic analyses for determining the cause of congenital anomalies and provide a useful genetic counseling. In addition, due to the fact that some of mosaic trisomy 22 features are unavoidable such as CHD and general hypotrophy, we suggest including echocardiography test for early diagnosis during the clinical assessment.
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http://dx.doi.org/10.1002/jcla.22663DOI Listing
February 2019

Self-Expanding Versus Balloon-Expandable Stents in Patients With Isthmic Coarctation of the Aorta.

Am J Cardiol 2018 09 27;122(6):1062-1067. Epub 2018 Jun 27.

Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada.

Endovascular stent implantation has become the treatment of choice for the management of patients with native coarctation of the aorta (CoA). The aim of this study was to compare the outcomes of self-expandable stenting (SES) with balloon-expandable stenting (BES) in the treatment of native CoA. In this single-center retrospective study, all patients who underwent SES or BES for the management of native CoA were enrolled. Patients were followed up for a median period of 35 (inter-quartile range 15 to 71) months. The primary outcome of interest was a composite end point consisted of death, surgical repair, re-stenting, re-ballooning, and hospital admission for hypertension crisis. The CoA diameter has changed from 3.2 ± 2.1 to 14.2 ± 4.0 mm in the BES group and from 4.6 ± 2.6 to 12.2 ± 3.7 mm in the SES group (both p <0.001). The procedure was successful with residual pressure gradient <20 mm Hg in 99.0% and 98.6% of patients in the BES and SES groups, respectively. Major adverse events occurred in 6 (8.7%) in the SES groups and 14 (20.3%) in the BES group (p = 0.053). Kaplan-Meier curve showed no difference between the 2 groups in terms of survival from major adverse events (p = 0.10), but when groups were matched for the propensity of stenting methods, SES was associated with lower major adverse events (p = 0.01). In conclusion, the SES and BES methods were safe and durable in our cohort with low rates of adverse events. After adjustment for the propensity of treatment with each stenting method, SES was associated with better outcomes. Regardless of the outcome of each method, it should be noted that the taken approach should be tailored to the patient's anatomy.
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http://dx.doi.org/10.1016/j.amjcard.2018.06.005DOI Listing
September 2018

Correction to: Clopidogrel Pharmacogenetics in Iranian Patients Undergoing Percutaneous Coronary Intervention.

Cardiovasc Toxicol 2018 10;18(5):492

Medical Genetics Laboratory, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Valiasr Street, Niyaesh Intersection, Tehran, 1995614331, Iran.

The original version of this article unfortunately contained a typo in the co-author name.
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http://dx.doi.org/10.1007/s12012-018-9475-xDOI Listing
October 2018

A novel mutation and intrafamilial phenotypic variability in ARVC/D.

Med J Islam Repub Iran 2018 6;32. Epub 2018 Feb 6.

Cardiogenetic Research Laboratory, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.

Arrhythmogenic ventricular cardiomyopathy (AVC) is an inherited cardiac disorder affecting 1 in 1000 individuals worldwide. The mean diagnosed age of disease is 31 years. In this article, an Iranian family reported that they were affected by ARVC due to a novel mutation. Clinical evaluations, 12-lead ECG, CMR, and signal-averaged ECG were performed. After DNA extraction, genetic testing was done, and PCR-sequencing was applied to find causal mutations. Segregation analysis was also performed for the family. ARVC criteria were documented in the patients. Genetic testing revealed a novel chain termination mutation (p.Tyr168Ter) in gene; this mutation was transmitted from the mother to her 23-year-old son, but only the son was affected with ARVC. Modifier genes were indicated using interactome analysis of Plakophilin 2 protein (); they might have led to phenotypic variability through cellular mechanisms, such as nonsense-mediated mRNA decay. At least, 9 proteins were identified that might have affected Plakophilin 2 protein function, and consequently, rationalizing this intrafamilial phenotypic variability. This study highlighted the role of modifier genes involved in ARVC as well as the major role of mutation in developing the disease in our population.
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http://dx.doi.org/10.14196/mjiri.32.5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6025913PMC
February 2018

Clopidogrel Pharmacogenetics in Iranian Patients Undergoing Percutaneous Coronary Intervention.

Cardiovasc Toxicol 2018 10;18(5):482-491

Medical Genetics Laboratory, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Valiasr Street, Niyaesh Intersection, Tehran, 1995614331, Iran.

Clopidogrel is used in patients with coronary syndromes and at risk of thrombotic events or receiving percutaneous coronary intervention (PCI) for reducing heart attack and stroke. Here we present genotype and phenotype study of Iranian patients undergoing PCI treated with clopidogrel during a 6-month period of follow-up; common variants of CYP2C19, CYP3A5, CYP3A4, and ABCB1 genes were determined as well as the patients' cardiovascular outcomes to find out the effect of these variants individually and in combination. 388 individuals receiving PCI were enrolled in this study. Different pretreatment doses of clopidogrel were prescribed under the interventional cardiologists' guidance. The patients were followed for a duration of 1 month, and 6 months. Six SNPs were selected for genotyping including CYP2C19*2 (c.681G > A), CYP2C19*3 (c.636G > A), CYP2C19*17 allele (c.-806C > T), ABCB1 (c.3435C > T), CYP3A5 (c.6986A > G), and CYP3A4 (c.1026 + 12G > A). The mean loading dose was 600 mg/day in 267 (68.8%) individuals, 300 mg/day in 121 (31.2%). 8 patients had cardiovascular events such as thrombosis, unstable angina, and non-STEMI. The studied alleles and genotypes were in Hardy-Weinberg equilibrium. None of the SNPs individually were significantly associated with outcome events. Our results indicate that combinations of different alleles of genes are involved in pharmacokinetic variability and joint factors are important; this means that genotyping and analysis of an individual variant may not be as straightforward in risk assessment and pharmacogenetics. This highlights the importance of personalized medicine in risk assessment and treatment.
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http://dx.doi.org/10.1007/s12012-018-9459-xDOI Listing
October 2018

Genotypic effect of a mutation of the MYBPC3 gene and two phenotypes with different patterns of inheritance.

J Clin Lab Anal 2018 Jul 1;32(6):e22419. Epub 2018 Mar 1.

Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.

Background: MYBPC3 mutations have been described in dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). A mutation, c.3373G>A, has been reported to cause autosomal recessive form of HCM. Here, we report that this mutation can cause autosomal dominant form of DCM.

Methods: Next-generation sequencing using targeted panel of a total of 23 candidate genes and following Sanger sequencing was applied to detect causal mutations of DCM. Computational analyses were also performed using available software tools. In silico structural and functional analyses including protein modeling and prediction were done for the mutated MYBPC3 protein.

Results And Conclusion: Targeted sequencing showed one variant c.3373G>A (p.Val1125Met) in the studied family following autosomal dominant inheritance. Computational programs predicted a high score of pathogenicity. Secondary structure of the region surrounding p.Val1125 was changed to a shortened beta-strand based on prediction of I-TASSER and Phyre2 servers with high confidence value for the mutation. cMyBP-C protein was modeled to 3dmkA. Our findings suggest that one single mutation of MYBPC3 may have different effects on the cellular mechanisms based of its zygosity. Various factors might be considered for explaining this phenomenon. This gene may have an important role in Iranian DCM and HCM patients.
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http://dx.doi.org/10.1002/jcla.22419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817065PMC
July 2018

Genotype, phenotype and in silico pathogenicity analysis of HEXB mutations: Panel based sequencing for differential diagnosis of gangliosidosis.

Clin Neurol Neurosurg 2018 04 8;167:43-53. Epub 2018 Feb 8.

Genetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran; Growth and Development Research, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Objectives: Gangliosidosis is an inherited metabolic disorder causing neurodegeneration and motor regression. Preventive diagnosis is the first choice for the affected families due to lack of straightforward therapy. Genetic studies could confirm the diagnosis and help families for carrier screening and prenatal diagnosis. An update of HEXB gene variants concerning genotype, phenotype and in silico analysis are presented.

Patients And Methods: Panel based next generation sequencing and direct sequencing of four cases were performed to confirm the clinical diagnosis and for reproductive planning. Bioinformatic analyses of the HEXB mutation database were also performed.

Results: Direct sequencing of HEXA and HEXB genes showed recurrent homozygous variants at c.509G>A (p.Arg170Gln) and c.850C>T (p.Arg284Ter), respectively. A novel variant at c.416T>A (p.Leu139Gln) was identified in the GLB1 gene. Panel based next generation sequencing was performed for an undiagnosed patient which showed a novel mutation at c.1602C>A (p.Cys534Ter) of HEXB gene. Bioinformatic analysis of the HEXB mutation database showed 97% consistency of in silico genotype analysis with the phenotype. Bioinformatic analysis of the novel variants predicted to be disease causing. In silico structural and functional analysis of the novel variants showed structural effect of HEXB and functional effect of GLB1 variants which would provide fast analysis of novel variants.

Conclusions: Panel based studies could be performed for overlapping symptomatic patients. Consequently, genetic testing would help affected families for patients' management, carrier detection, and family planning's.
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http://dx.doi.org/10.1016/j.clineuro.2018.02.011DOI Listing
April 2018

Pathogenic significance of SCN1A splicing variants causing Dravet syndrome: Improving diagnosis with targeted sequencing for variants by in silico analysis.

Clin Neurol Neurosurg 2018 03 31;166:80-90. Epub 2018 Jan 31.

Genetic Research Laboratory, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Objectives: Genetic heterogeneity of epileptic encephalopathy (IEE) mandates the use of gene-panels for diagnosis.

Patients And Methods: A 36-gene-panel next-generation sequencing was applied for IEE in two Iranian families. A literature search was performed using keywords to identify reported splicing mutations in SCN1A and perform genotype-phenotype correlation.

Results: An update of splicing mutations revealed 147 variants with 65.75% of them de novo mutations. Most of the familial variants were of parental origin. The structure of the protein was often affected in the linker and transmembrane segments. 92% of intronic variants were pathogenic. A de novo heterozygous mutation was found in the first patient, but not in her sibling and parents. In the second family, a novel de novo heterozygous mutation was found at position c.1210insT leading to a truncated protein.

Conclusion: Gene-panel sequencing is helpful for reducing the time and cost, guiding early treatment, and estimating the recurrence risks. The importance of characterization of intronic variants was noticed; though bioinformatics analysis of novel intronic variants should be of concern for rapid reporting the pathogenic effect of variants.
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http://dx.doi.org/10.1016/j.clineuro.2018.01.030DOI Listing
March 2018