Publications by authors named "Ladan Sadeghian"

9 Publications

  • Page 1 of 1

Determining genetic variants in children and adolescents suffering from tetralogy of Fallot with a positive family history: methodology.

Acta Biomed 2020 06 26;91(4):e2020096. Epub 2020 Jun 26.

Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.

Background And Aim: Congenital heart disease (CHD) affects near 1% of all live births and is considered to be the main reason of morbidity and mortality in early childhood. In this study, we investigated molecular genetics factors associated with Tetralogy of Fallot (TOF) using high throughput technologies in the consanguineous families with at least 2 affected individual.

Method: This family study started in March 2017 to May 2018 in pediatric cardiovascular research center, Cardiovascular Research Institute, Isfahan, Iran. After obtaining informed consent, we invited families who had at least 2 individuals in one generation or previous generations with familial marriage history and they were included in the study. Genomic DNA was extracted from peripheral blood lymphocytes of the patient and samples were investigated for structural variations such as deletion or duplication in the genome using single nucleotide polymorphism array (SNP array). In the next step, if the SNP array is negative, next generation study will be performed in the propend and after analyzing the raw data and filtering for rare pathogenic variants.

Results: In this study, totally 5 families were evaluated. All affected and unaffected individuals of each family included in the pedigree.  This study comprised 14 subjects (9 males and 5 females; 8.92 ± 6.21 years old). Baseline characteristics and clinical data of the study subjects are presented in Table 1. The prevalence of consanguineous marriage is 92.2% among parents, 71.4% among mother grandparents and 28.6% among father grandparents. 64.3 % of our participants have sibling with similar disease. The prevalence of atrial septal defect (ASD), ventricular septal defect (VSD), and arrhythmia and TOF was 7.1%.

Conclusion: We found some families with 2 or more CHD and with a high rate of consanguineous marriage and probably suffering from a genetic predisposition. We aim to exam them further with next generation study (NGS) to find any genetic defect and then to exam other CHD's in our region. Key words: gene mutations, children, adolescents, tetralogy of Fallot, family history.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.23750/abm.v91i4.8410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927530PMC
June 2020

The Epigenetic Overlap between Obesity and Mood Disorders: A Systematic Review.

Int J Mol Sci 2020 Sep 15;21(18). Epub 2020 Sep 15.

MPH Program, School of Public Health, Central Michigan University, Mount Pleasant, MI 48859, USA.

(1) Background: Obesity and mood disorders are considered as the most prevalent morbidities in many countries. We suppose that epigenetic mechanisms may induce higher rates of obesity in subjects who suffer from mood disorders. In this systematic review, we focused on the potential roles of DNA methylation on mood disorders and obesity development. (2) Methods: This systematic review was conducted in accordance with the PRISMA statement and registered in Prospero. A systematic search was conducted in MEDLINE, Scopus, Web of Science, Cochrane Central database, EMBASE, and CINHAL. We also conducted a Grey literature search, such as Google Scholar. (3) Results: After deduplication, we identified 198 potentially related citations. Finally, ten unique studies met our inclusion criteria. We have found three overlap genes that show significant DNA methylation changes, both in obesity and depression. Pathway analysis interaction for , and confirmed the relation of these genes in both obesity and mood disorders. (4) Conclusions: While mechanisms linking both obesity and mood disorders to epigenetic response are still unknown, we have already known chronic inflammation induces a novel epigenetic program. As the results of gene enrichment, pathways analysis showed that and linked together by inflammatory pathways. Hypermethylation in these genes might play a crucial rule in the co-occurrence of obesity and mood disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21186758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555814PMC
September 2020

Isfahan Twins Registry (ITR): An Invaluable Platform for Epidemiological and Epigenetic Studies: Design and Methodology of ITR.

Twin Res Hum Genet 2019 12 20;22(6):579-582. Epub 2020 Jan 20.

Pediatric Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Science, Isfahan, Iran.

Twin studies are one of the main tools for studying the interaction between genes and the environment in the development of complex diseases such as cancers, cardiovascular diseases and diabetes. The Isfahan Twin Registry (ITR) was launched in Isfahan in 2017 as a pilot study to establish a nationwide twin registry in Iran and aims to obtain comprehensive information about complex diseases and their risk factors from twins and multiples living in Isfahan. ITR will continue to recruit twins and multiples until all twins residing in Isfahan are registered in the registry. Twins are identified from welfare agencies, public health homes, maternity hospitals, Persian Twins Association and the local media. Demographic information, twin similarities, lifestyle, family history of diseases and past medical history are collected using validated questionnaires. Anthropometric measurements and blood pressure are measured by health professionals. Hematology panel, fasting blood sugar, total cholesterol, low-density lipoprotein, high-density lipoprotein, aspartate aminotransferase, alanine aminotransferase and quantitative C-reactive protein are measured by an automated analyzer. Extra samples are obtained for future studies. For twins aged under 6 years, parents complete the questionnaires for their children and a brief questionnaire for themselves. Currently, 998 persons (395 pairs and 67 multiples) are registered in the ITR and have provided their data. Results of preliminary data analysis are discussed in this article. We plan to carry out longitudinal assessments. ITR can play an important role in future epigenetic, biomarkers and omics studies using the biobank materials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/thg.2019.119DOI Listing
December 2019

MicroRNAs as the actors in the atherosclerosis scenario.

J Physiol Biochem 2020 Feb 5;76(1):1-12. Epub 2019 Dec 5.

Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.

Atherosclerosis is considered as the most common cardiovascular disease and a leading cause of global mortality, which develops through consecutive steps. Various cellular and molecular biomarkers such as microRNAs are identified to be involved in atherosclerosis progression. MicroRNAs are a group of endogenous, short, non-coding RNAs, which are able to bind to specific sequences on target messenger RNAs and thereby modulate gene expression post-transcriptionally. MicroRNAs are key players in wide range of biological processes; thus, their expression level is regulated in pathophysiological conditions. Ample evidences including in vitro and in vivo studies approved a critical role of microRNAs in epigenetic and the sequential processes of atherosclerosis from risk factors to plaque formation, progression, and rupture. Based on these findings, miRNAs seems to be promising candidates for therapeutic approach. This review summarizes the role of miRNAs in atherosclerosis development, epigenetic, and therapy. Moreover, the application of exosomes in miRNA delivery, and/or their prognostic and diagnostic values are also discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13105-019-00710-7DOI Listing
February 2020

Next-generation sequencing reveals a novel pathological mutation in the TMC1 gene causing autosomal recessive non-syndromic hearing loss in an Iranian kindred.

Int J Pediatr Otorhinolaryngol 2019 Sep 21;124:99-105. Epub 2019 May 21.

Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran. Electronic address:

Objectives: Hearing loss (HL) is the most common sensory-neural disorder with excessive clinical and genetic heterogeneity, which negatively affects life quality. Autosomal recessive non-syndromic hearing loss (ARNSHL) is the most common form of the disease with no specific genotype-phenotype correlation in most of the cases. Whole exome sequencing (WES) is a powerful tool to overcome the problem of finding mutations in heterogeneous disorders.

Methods: A comprehensive clinical and pedigree examination was performed on a multiplex family from Khuzestan province suffering from hereditary HL. Direct sequencing of GJB2 and genetic linkage analysis of DFNB1A/B was accomplished. WES was utilized to find possible genetic etiology of the disease. Co-segregation analysis of the candidate variant was done. High resolution melting analysis was applied to detect variant status in 50 healthy matched controls.

Results: Clinical investigations suggested ARNSHL in the pedigree. The family was negative for DFNB1A/B. WES revealed a novel nonsense mutation, c.256G > T (p.Glu86*), in TMC1 segregating with the phenotype in the pedigree. The variant was absent in the controls.

Conclusion: Here, we report successful application of WES to identify the molecular pathogenesis of ARNSHL in a large family. The novel nonsense TMC1 variant meets the criteria of being pathogenic according to the ACMG-AMP variant interpretation guideline.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijporl.2019.05.023DOI Listing
September 2019

Applying Two Different Bioinformatic Approaches to Discover Novel Genes Associated with Hereditary Hearing Loss via Whole-Exome Sequencing: ENDEAVOUR and HomozygosityMapper.

Adv Biomed Res 2018 31;7:141. Epub 2018 Oct 31.

Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: Hearing loss (HL) is a highly prevalent heterogeneous deficiency of sensory-neural system with involvement of several dozen genes. Whole-exome sequencing (WES) is capable of discovering known and novel genes involved with HL.

Materials And Methods: Two pedigrees with HL background from Khuzestan province of Iran were selected. Polymerase chain reaction-sequencing of and homozygosity mapping of 16 DFNB loci were performed. One patient of the first and two affected individuals from the second pedigree were subjected to WES. The result files were analyzed using tools on Ubuntu 16.04. Short reads were mapped to reference genome (hg19, NCBI Build 37). Sorting and duplication removals were done. Variants were obtained and annotated by an online software tool. Variant filtration was performed. In the first family, ENDEAVOUR was applied to prioritize candidate genes. In the second family, a combination of shared variants, homozygosity mapping, and gene expression were implemented to launch the disease-causing gene.

Results: sequencing and linkage analysis established no homozygosity-by-descent at any DFNB loci. Utilizing ENDEAVOUR, : C.C857G (.A286G), and : C.C5557T (.R1853C) were put forward, but none of the variants co-segregated with the phenotype. Two genes, and , were prioritized in the homozygous regions detected by HomozygosityMapper.

Conclusion: WES is regarded a powerful approach to discover molecular etiology of Mendelian inherited disorders, but as it fails to enrich GC-rich regions, incapability of capturing noncoding regulatory regions and limited specificity and accuracy of copy number variations detection tools from exome data, it is assumed an insufficient procedure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/abr.abr_80_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6233028PMC
October 2018

Differential expression of CCL18 in moderate/severe and mild persistent allergic rhinitis and its correlation with disease parameters.

J Immunoassay Immunochem 2018 13;39(5):485-495. Epub 2018 Aug 13.

d Faculty of Medicine , Tehran University of Medical Sciences , Tehran , Iran.

Background And Aims: This study aimed to assess the level of the expression of CCL-18 on nasal inferior turbinate mucosa in patients with mild (M) and moderate-to-severe (M/S) persistent allergic rhinitis (PAR).

Methods: The participants in this case-controlled study were divided into three groups: patients with M/S PAR, patients with M PAR, and the healthy control group. Biopsies of nasal inferior turbinate mucosa were obtained from the participants. Expression of CCL-18 mRNA was evaluated by real-time PCR. The serum levels of CCL-18 were determined by ELISA. Total serum IgE levels and specific serum IgE levels were measured. The clinical manifestations were assessed using the total nasal syndrome score (TNSS).

Results: Gene expression and the serum level of CCL-18 in patients with M/S PAR increased significantly compared to the control group and patients with M PAR. The serum level of CCL-18 was found to correlate with TNSS in patients with M/S PAR. There was a statistical correlation between the serum level of CCL-18 and the total serum IgE in the treatment groups.

Conclusion: The results of the study indicate that there could be a relationship between the expression of CCL-18 in nasal turbinate mucosa and the severity of allergic rhinitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15321819.2018.1506931DOI Listing
October 2018

Alteration in CD8 T cell subsets in enterovirus-infected patients: An alarming factor for type 1 diabetes mellitus.

Kaohsiung J Med Sci 2018 May 20;34(5):274-280. Epub 2018 Jan 20.

Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Type 1 diabetes is a multi-factorial disease that can develop due to the combination of genetic and environmental factors. Viruses, particularly enteroviruses, are major environmental candidates in the pathogenesis of type 1 diabetes, even though the mechanisms of pathogenicity of these viruses and their effects on the immune system have not been understood very well yet. Previous studies show that any imbalance in the population of different lymphocyte subsets could develop autoimmune diseases. Our theory is that enteroviral infection causes an impairment in the distribution of lymphocyte subtypes and consequently results in the diabetes onset in some individuals. Therefore, in this project, we evaluated the distribution of T CD8+ lymphocytes and their subsets in type 1 diabetes patients. This study was conducted to investigate the relationship between enteroviral infection and type 1 diabetes mellitus in an Iranian population, and suggestion a predicting approach for susceptible subjects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.kjms.2017.12.010DOI Listing
May 2018