Publications by authors named "Samira Kalayinia"

8 Publications

  • Page 1 of 1

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

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

A comprehensive in silico analysis, distribution and frequency of human mutations; A critical gene in congenital heart disease.

J Cardiovasc Thorac Res 2019 31;11(4):287-299. Epub 2019 Oct 31.

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

Congenital heart disease (CHD) affects 1% to 2 % of live births. The gene, is known as the significant heart marker during embryonic evolution and it is also necessary for the survival of cardiomyocytes and homeostasis in adulthood. In this study, mutations are investigated to identify the frequency, distribution, functional consequences of mutations by using computational tools. A complete literature search was conducted to find mutations using the following key words: and/or CHD and mutations. The mutations were in silico analyzed using tools which predict the pathogenicity of the variants. A picture of protein and functional or structural effects of its variants were also figured using I-TASSER and STRING. A total number of 105 mutations from 18 countries were introduced. The most (24.1%) and the least (1.49%) frequency of mutations were observed in Europe and Africa, respectively. The c.73C>T and c.533C>T mutations are distributed worldwide. c.325G>T (62.5%) and c.896A>G (52.9%) had the most frequency. The most numbers of mutations were reported from Germany. The c.541C>T had the highest CADD score (Phred score = 38) and the least was for c.380C>A (Phred score=0.002). 41.9% of mutations were predicted as potentially pathogenic by all prediction tools. This is the first report of the mutations evaluation in the worldwide. Given that the high frequency of mutation in Germany, and also some mutations were seen only in this country, therefore, presumably the main origin of mutations arise from Germany.
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http://dx.doi.org/10.15171/jcvtr.2019.47DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6891041PMC
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

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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938395PMC
February 2019

Next generation sequencing applications for cardiovascular disease.

Ann Med 2018 03 26;50(2):91-109. Epub 2017 Oct 26.

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

The Human Genome Project (HGP), as the primary sequencing of the human genome, lasted more than one decade to be completed using the traditional Sanger's method. At present, next-generation sequencing (NGS) technology could provide the genome sequence data in hours. NGS has also decreased the expense of sequencing; therefore, nowadays it is possible to carry out both whole-genome (WGS) and whole-exome sequencing (WES) for the variations detection in patients with rare genetic diseases as well as complex disorders such as common cardiovascular diseases (CVDs). Finding new variants may contribute to establishing a risk profile for the pathology process of diseases. Here, recent applications of NGS in cardiovascular medicine are discussed; both Mendelian disorders of the cardiovascular system and complex genetic CVDs including inherited cardiomyopathy, channelopathies, stroke, coronary artery disease (CAD) and are considered. We also state some future use of NGS in clinical practice for increasing our information about the CVDs genetics and the limitations of this new technology. Key messages Traditional Sanger's method was the mainstay for Human Genome Project (HGP); Sanger sequencing has high fidelity but is slow and costly as compared to next generation methods. Within cardiovascular medicine, NGS has been shown to be successful in identifying novel causative mutations and in the diagnosis of Mendelian diseases which are caused by a single variant in a single gene. NGS has provided the opportunity to perform parallel analysis of a great number of genes in an unbiased approach (i.e. without knowing the underlying biological mechanism) which probably contribute to advance our knowledge regarding the pathology of complex diseases such as CVD.
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http://dx.doi.org/10.1080/07853890.2017.1392595DOI Listing
March 2018

Extracellular matrix protein 1 gene (ECM1) mutations in nine Iranian families with lipoid proteinosis.

Indian J Med Res 2016 Mar;143(3):303-7

Department of Clinical Genetic, NIGEB, Tehran, Iran.

Background & Objectives: Lipoid proteinosis (LP) is an autosomal recessive disease. Clinical characteristics of this disease are hoarse voice, scarring of the skin, brain calcifications, and eyelid papules (moniliform blepharosis). Mutations in the ECM1 gene on 1q21.2 are responsible for this disease. This study was conducted to investigate the mutation spectrum of ECM1 gene in nine Iranian families having at least one LP patient diagnosed clinically.

Methods: The entire ECM1 gene was screened using PCR and direct sequencing in nine Iranian families with 12 suspected LP patients who were referred to the clinic, along with their parents and siblings. Thirty healthy individuals were included as controls.

Results: In only one patient a homozygous G>A transition at nucleotide c.806 in exon 7 was detected. A G>A substitution at nucleotide 1243 in exon 8 that changes glycine (GGT) to serine (AGT) was observed in most of our patients. Furthermore, in one patient there was a change in the sequence of intron 8, the A>T transition in nucleotide 4307. In addition, in two cases (one patient and one healthy mother with affected child) there was a C (4249) deletion in intron 8.

Interpretation & Conclusions: Our results indicate that although mutation in ECM1gene is responsible for lipoid proteinosis, it is likely that this is not the only gene causing this disease and probably other genes may be involved in the pathogenesis of the LP disease.
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http://dx.doi.org/10.4103/0971-5916.182620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4892076PMC
March 2016

Association between the atrial natriuretic peptide rs5065 gene polymorphism and the presence and severity of coronary artery disease in an Iranian population.

Coron Artery Dis 2014 May;25(3):242-6

Department of Pathology, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.

Objective: The atrial natriuretic peptide (ANP) gene expression and some of its related single-nucleotide polymorphisms have been well established as a characterized biomarker of cardiovascular diseases. In the present study, we aimed to evaluate the potential association between one of the introduced ANP gene polymorphisms of 2238 T/C (rs5065) with coronary artery disease (CAD) in an Iranian population.

Basic Methods: A total of 573 patients with CAD according to angiography reports and 293 controls without any evidence of CAD were enrolled. Allelic discrimination of the single-nucleotide polymorphism rs5065 in both groups was performed using a High Resolution Melt technique in real-time PCR analysis.

Main Results: With respect to the prevalence of different genotypes of rs5065 polymorphism, the frequency of the T allele in the CAD group was significantly lower in CAD than that in the non-CAD group (59.7 vs. 65.1%, P=0.032). A significant inverse association was also found between the frequency of T allele and severity of CAD assessed by the Gensini score; the average of this score in T-allele carriers was 38.6±41.6 and that in C-allele carriers was 57.7±46.3 (P≤0.0001). Using multivariable linear regression modeling with the presence of baseline variables, the presence of the rs5065 ANP T allele could predict decreased severity of CAD assessed by the Gensini score in our population.

Principal Conclusion: The presence of the rs5065 ANP polymorphism is potentially associated with a reduced risk of CAD as well as with reduced severity of CAD independent of the general risk factors of CAD.
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http://dx.doi.org/10.1097/MCA.0000000000000075DOI Listing
May 2014