Publications by authors named "Majid Kheirollahi"

50 Publications

Gene expression profiles of YAP1, TAZ, CRB3, and VDR in familial and sporadic multiple sclerosis among an Iranian population.

Sci Rep 2021 Apr 8;11(1):7713. Epub 2021 Apr 8.

Isfahan Neuroscience Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Alterations in the regulatory mechanisms that control the process of myelination in the nervous system, may lead to the impaired myelination in the Multiple sclerosis. The Hippo pathway is an important mediator of myelination in the nervous system and might contribute to the pathophysiology of MS. This study examined via qPCR the RNA expression of YAP1, TAZ, and CRB3 as the key effectors of the Hippo pathway and also, VDR in the peripheral blood of 35 sporadic, 37 familial MS patients; and also 34 healthy first-degree relatives of the familial MS patients (HFR) and 40 healthy individuals without a family history of the disease (control). The results showed the increased expression of VDR in the sporadic group, as compared to other groups. There was also an increased expression of TAZ in the familial and HFR groups, as compared to the control group. The familial and sporadic patients displayed a significantly lower level of expression of YAP1 in comparison to the HFR group. The increased expression level in the sporadic patients and control group, as compared to the HFR group, was seen in CRB3. We also assessed different clinical parameters and MRI characteristics of the patients. Overall, these findings suggest that Hippo pathway effectors and also VDR gene may play a potential role in the pathophysiology of the sporadic and familial forms of MS. Confirmation of different gene expression patterns in sporadic and familial MS groups may have obvious implications for the personalization of therapies in the disease.
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http://dx.doi.org/10.1038/s41598-021-87131-zDOI Listing
April 2021

Homozygous TFG gene variants expanding the mutational and clinical spectrum of hereditary spastic paraplegia 57 and a review of literature.

J Hum Genet 2021 Mar 25. Epub 2021 Mar 25.

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

In recent years, the tropomyosin-receptor kinase fused gene (TFG) has been linked to diverse hereditary neurodegenerative disorders, including a very rare complex hereditary spastic paraplegia, named spastic paraplegia type 57 (SPG57). Until now, four pathogenic homozygous variants of the TFG gene have been reported associated with SPG57. Two consanguineous Iranian families (1 and 2), the first one with two affected members and the second one with one, all with an early-onset progressive muscle weakness, spasticity, and several neurological symptoms were examined via the whole-exome sequencing. Two homozygous missense variants including c.41A>G (p.Lys14Arg) and c.316C>T (p.Arg106Cys) have been found in the related families. The candidate variants were confirmed by Sanger sequencing and found to co-segregate with the disease in families. The bioinformatics analysis showed the deleterious effects of these nucleotide changes and the variants were classified as pathogenic according to ACMG guidelines. A comparison of the clinical presentation of the patients harboring c.41A>G (p.Lys14Arg) with previously reported SPG57 revealed variability in the severity state and unreported clinical presentation, including, facial atrophy, nystagmus, hyperelastic skin, cryptorchidism, hirsutism, kyphoscoliosis, and pectus excavatum. The affected member of the second family carried a previously reported homozygous c.316C>T (p.Arg106Cys) variant and displayed a complex HSP including optic atrophy. Remarkable clinical differences were observed between the family 1 and 2 harboring the c.41A>G (p.Lys14Arg) and c.316C>T (p.Arg106Cys) variants, which could be attributed to the distinct affected domains (PB1 domains and coiled-coil domains), and therefore, SPG57 might have been representing phenotype vs. variant position correlation.
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http://dx.doi.org/10.1038/s10038-021-00919-9DOI Listing
March 2021

Identification of a Missense Variant in the EIF2B3 Gene Causing Vanishing White Matter Disease with Antenatal-Onset but Mild Symptoms and Long-Term Survival.

J Mol Neurosci 2021 Mar 9. Epub 2021 Mar 9.

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

Vanishing white matter disease (VWM) is a rare autosomal recessive leukodystrophy caused by a mutation in any of the five gene encoding subunits of the translation initiation factors eIF2B1 to eIF2B5. Whole-exome sequencing was performed on a 7-year-old boy with prenatal symptoms, including intrauterine-growth retardation, decreased movements, and oligohydramnios as well as mild intellectual disability, optic atrophy, macrocephaly, mild ataxia, and white matter lesions after birth. Analysis of WES data revealed a homozygous missense variant, c.C590T (p.Thr197Met) in the EIF2B3 gene (NM_0203650). The candidate variant was confirmed by Sanger sequencing and found to co-segregate with disease in family members. Pathogenicity analysis, 3D protein modeling, and stability assessment showed the deleterious effects of this nucleotide change. Previous studies suggest a direct relationship between the onset of symptoms and the progression rate and severity of the disease. All described cases of EIF2B deficiency with antenatal-onset led prenatal death; if they were born, they experienced clinical exacerbation, seizure, severe encephalopathy, and consequent infantile death (< 1 year). The patient of this study had never had seizure, which could be a potential explanation for the observed mild clinical picture, chronic state, and long-term survival until the age of seven. This study reported the first VWM due to EIF2B gene deficiency with antenatal-onset but mild symptoms and long-term survival. The result of this study showed that stressor factors, particularly seizure, could have a substantial role in poor prognosis and early neonatal death.
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http://dx.doi.org/10.1007/s12031-021-01810-0DOI Listing
March 2021

An interdependence between GAPVD1 gene polymorphism, expression level and response to interferon beta in patients with multiple sclerosis.

J Neuroimmunol 2021 Apr 30;353:577507. Epub 2021 Jan 30.

Department of Medical Genetics, Faculty of Medicine, Tabriz university of Medical Sciences, Tabriz, Iran. Electronic address:

Interferon-β (IFN-β) is among the first drugs used for reducing the symptoms of multiple sclerosis (MS). Many studies show that the genetic predisposition of patients might modulate their response to IFN-β treatment. In this study GAPVD1 gene expression and the genotyping of rs2291858 variant were analysed in 100 responder and 100 non-responder patients with MS treated using IFN-β. Moreover, rs2291858 genotyping was performed for 200 patients with MS and 200 healthy controls. GAPVD1 expression was significantly increased in the responder patients than in non-responders and the distribution of rs2291858 polymorphism was significantly different between them. The GAPVD1 expression level in AA genotype of the responder group was higher than that in other genotypes of these two groups. The results show that the GAPVD1 expression level and rs2291858 genotype probably affect the response to IFN- β in patients with MS.
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http://dx.doi.org/10.1016/j.jneuroim.2021.577507DOI Listing
April 2021

The Effect of Parental Consanguinity on Clinical Course and Outcome of Children with Focal Segmental Glomerulosclerosis, a Report from Isfahan, Iran.

Iran J Kidney Dis 2020 Sep;14(5):348-357

Isfahan Kidney Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Introduction: Focal segmental glomerulosclerosis (FSGS) accounts for 20% of nephrotic syndromes among children as well as 75% of the steroid resistant nephrotic syndrome (SRNS). The aim of the present study was to evaluate the influence of parental consanguinity on clinical course and outcome of FSGS in children.

Methods: This historical cohort was carried out on 69 children affected by steroid resistant FSGS. Patients' data were recorded at the initial and the final analyses and response to therapeutic measures. Subjects were also questioned about the history of parental consanguinity.

Results: Forty-four participants (63.8%) were male with a male to female proportion of 1.76:1. Mean baseline age was 5.69 ± 2.39 (range: 1 to 10). Fifty-one patients (73.9%) reported consanguinity. A more significant resistance to cyclosporine A and cyclophosphamide was observed in participants denoting parental consanguinity than those with no kinship. The average renal survival time obtained significantly lower among those reporting consanguinity compared to the others (8.33 vs. 10.44 years, P < .05). According to univariate analysis results, parental consanguinity was a risk factor for developing chronic kidney disease (HR = 4.56, 95% CI: 1.06 to 19.47; P < .05).

Conclusion: Patients with FSGS plus parental consanguinity presented less renal survival time with more resistance to cures being more predisposed to the development of CKD.
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September 2020

The Clinical Effectiveness of Preimplantation Genetic Diagnosis for Chromosomal Translocation Carriers: A Meta-analysis.

Glob Med Genet 2020 Jun 8;7(1):14-21. Epub 2020 Jul 8.

Department of Genetics and Molecular Biology, School of Medicine, Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran.

Published data on the relationship between pregnancy outcomes of preimplantation genetic diagnosis (PGD) in translocation carriers have implicated inconclusive results. To identify potentially eligible reports, an electronic search was conducted in several databases, including PubMed, Scopus, Web of Knowledge, and Cochrane. Pooled odd ratios (ORs) and 95% confidence intervals (Cis) were estimated based on a random-effect model to evaluate the strength of association between PGD and successful pregnancy outcome in translocation carriers. A total of six cohort studies were included in the current study. The meta-analysis of these studies revealed that the PGD method was associated with an increased successful pregnancy outcome of translocation carriers (OR = 8.58; 95%CI: 1.40-52.76). In subgroup analysis, there was no significant association according to the chromosomal translocation carrier origin and the type of translocated chromosomes, as well as country. In developed countries, the pregnancy outcome of PGD was significantly improved in translocation carriers (OR = 21.79; 95%CI: 1.93-245.52). The current meta-analysis demonstrated that the PGD method is associated with successful pregnancy outcome in both types of reciprocal and Robertsonian translocation carriers, especially in developed countries.
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http://dx.doi.org/10.1055/s-0040-1712455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410090PMC
June 2020

Meta-Analysis on the Association of C-Reactive Protein Polymorphisms with Metabolic Syndrome.

Glob Med Genet 2020 Jun 9;7(1):8-13. Epub 2020 Jul 9.

Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran.

Polymorphisms in the C-reactive protein (CRP) genes might have crucial role in the development of metabolic syndrome (MetS). In the current comprehensive meta-analyses, we aim to provide a quantitative assessment of the association between CRP single-nucleotide polymorphisms (SNPs) and the risk of MetS. An electronic search was performed on several databases. After data extraction, random effect model was used to calculate the pooled odds ratio (OR) and 95% confidence intervals (CIs). Four independent studies including case-control, cohort, and cross-sectional methods were analyzed. Our meta-analysis indicated that CRP polymorphisms are not significantly associated with MetS (OR = 0.92, 95% CI = 0.77-1.10) with significant heterogeneity (  = 55.4%; -value = 0.008). The subgroup analysis revealed that only GG has significant association with MetS (OR = 0.32, 95% CI = 0.13-0.80, -value = 0.015) without significant heterogeneity (  = 0%, -value > 0.05). In conclusion, this meta-analysis provides strong evidence that only some SNPs of CRP gene are associated with the risk for development of MetS; and this relationship does not exist in different ethnic populations.
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http://dx.doi.org/10.1055/s-0040-1710548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410104PMC
June 2020

A Novel Pathogenic Variant in NAGLU (N-Acetyl-Alpha-Glucosaminidase) gene Identified by Targeted Next-Generation Sequencing Followed by in Silico Analysis.

Iran J Child Neurol 2019 ;13(4):173-183

Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-communicable disease, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: Mucopolysaccharidosis IIIB (MPS IIIB) (Sanfilippo Syndrome Type B; OMIM 252920) is an autosomal recessive metabolic disorder caused by mutations in the gene which encode lysosomal enzyme N-acetyl-glucosaminidase, involved in degradation of complex polysaccharide, heparan sulfate. The disease is characterized by progressive cognitive decline and behavioral difficulties and motor function retardation.

Materials & Methods: In this study, targeted exome sequencing was used in consanguineous parent (mother) of a deceased child with clinical diagnosis of mucopolysaccharidosis. Sanger sequencing was performed to confirm the candidate pathogenic variants in extended family members and segregation analysis. In silico pathogenicity assessment of detected variant using multiple computational predictive tools were performed. Computational docking using the Molegro Virtual Docker (MVD) 6.0.1 software applied to evaluate affinity binding of altered protein for its ligand, N-Acetyl-D-Glucosamine. Moreover, with I-TASSER software functional alterations between wild and mutant proteins evaluated.

Results: We identified a novel heterozygote deletion variant (c.1294-1304 del CTCTTCCCCAA, p.432LeufsX25) in the gene. The variant was classified as pathogenic based on the American College of Medical Genetics and Genomics guideline. Computational docking with the Molegro Virtual Docker (MVD) 6.0.1 software confirmed different affinity binding of truncated protein for its ligand. Moreover, I-TASSER software revealed structural and functional alterations of mutant proteins.

Conclusion: This study expands the spectrum of pathogenic variants and confirms the utility of targeted NGS sequencing in genetic diagnosis and also the utility and power of additional family information.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789092PMC
January 2019

Clinical Feature and Genetics in Rett Syndrome: A Report on Iranian Patients.

Iran J Child Neurol 2019 ;13(4):37-51

Objectives: Rett syndrome is characterized by normal development for the first 6-18 months of life followed by the loss of fine and gross motor skills and the ability to engage in social interaction. In most patients, mutations are found in methyl CpG-binding protein 2 (MECP2) gene. We investigated the relation between Rett clinical diagnosis and mutations in MECP2.

Materials & Methods: Children suspected of Rett syndrome were invited to participate in this study. Twenty-three patients from the Mofid Hospital, Tehran, Iran suffered from classic Rett syndrome diagnostic criteria were enrolled in 2012. The severity of symptoms was assessed for all of them. The peripheral blood samples were collected in EDTA tubes and the genomic DNA was extracted using standard salting out method. The mutation of MEPC2 gene was studied using DNA sequencing method.

Results: Overall, 11(47.8%) patients had MECP2 gene mutation, while 12 cases (52.2%) had no mutations. Changes in genetics were associated with phenotypical manifestations. The most prevalent mutation was p.v288 mainly associated with partially or uncontrolled seizures.

Conclusion: For the first time, we studies the Rett syndrome in terms of clinical manifestations and genetic changes in Iran.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789083PMC
January 2019

Targeting MCF-7 Cell Line by Listeriolysin O Pore Forming Toxin Fusion with AHNP Targeted Peptide.

Adv Biomed Res 2019 27;8:33. Epub 2019 May 27.

Department of Immunology, Faculty of Medicine, Shahid Sadoughi University of Medical Science, Yazd, Iran.

Background: Tumor-targeting peptides are attracting subjects in cancer therapy. These peptides, which are widely studied, deliver therapeutic agents to the specific sites of tumors. In this study, we produced a new form of recombinant listeriolysin O (LLO) with genetically fused Anti-HER2/neu peptide (AHNP) sequence adding to its C-terminal end. The aim of the study was to engineer this pore-forming toxin to make it much more specific to tumor cells.

Materials And Method And Results: Two forms of the toxin (with and without peptide) were subcloned into a bacterial expression plasmid. Subcloning was performed using a polymerase chain reaction (PCR) product as a megaprimer in a quick-change PCR to introduce the whole insert gene into the expression plasmid. After expression of two recombinant forms of LLO in BL21 DE3 cells, purification was performed using Ni-NTA affinity column. MDA-MB-231 and MCF-7 cell lines (as negative and positive controls, respectively) were treated with both LLO toxins to evaluate their cytotoxicity and specificity. The IC of LLO on MDA-MB-231 and MCF-7 cells was 21 and 5 ng/ml, respectively. In addition, IC for the fusion AHNP-LLO toxin was 140 and 60 ng/ml, respectively. It was found that the cytotoxicity of the new engineered AHNP-LLO toxin has decreased by about 9x compared to the wild-type toxin and the specificity of the AHNP-LLO toxin has been also reduced.

Conclusions: Results show that the C-terminal of the LLO should not be modified and it seems that N-terminal of the toxin should be preferred for engineering and adding peptide modules.
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http://dx.doi.org/10.4103/abr.abr_18_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6543864PMC
May 2019

Mn-doped ZnS quantum dots-chlorin e6 shows potential as a treatment for chondrosarcoma: an in vitro study.

IET Nanobiotechnol 2019 Jun;13(4):387-391

Department of Medical Physics, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Chondrosarcoma is the second-most malignant cancer of the bone and routine treatments such as chemotherapy and radiotherapy have not responded to the treatment of this cancer. Due to the resistance of chondrosarcoma to radiotherapy, the combination of therapeutic methods has been considered in recent years. In this study, a novel combination approach is used that allows photodynamic therapy to be activated by X-rays. The synthesis of Mn-doped zinc sulphide (ZnS) quantum dots was carried out and chlorin e6 photosensitiser attached by covalent and non-covalent methods and their application as an intracellular light source for photodynamic activation was investigated. The toxicity of each nanoparticles was evaluated on chondrosarcoma cancer cells (SW1353) before and after radiation. Also, the effect nanoparticle-photosensitiser conjugated type was investigated in the therapeutic efficacy. The characterisation test (SEM, TEM, EDS, TGA, XRD and ICP analyses) was shown successful synthesis of Mn-doped ZnS quantum dots. Chondrosarcoma cancer cell viability was significantly reduced when cells were treated with MPA-capped Mn-doped ZnS quantum dots-chlorin e6 with spermine linker and with covalent attachment ( ≤ 0.001). These results indicate that X-ray can activate the quantum dot complexes for cancer treatment, which can be a novel method for treatment of chondrosarcoma.
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http://dx.doi.org/10.1049/iet-nbt.2018.5387DOI Listing
June 2019

The MTHFR C677T polymorphism influences the efficacy of folic acid supplementation on the nerve conduction studies in patients with diabetic polyneuropathy; A randomized, double blind, placebo-controlled study.

J Res Med Sci 2019 26;24:36. Epub 2019 Apr 26.

Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: Among patients with diabetic polyneuropathy, the status of folic acid, homocysteine, and nerve conduction studies (NCS) variations has been associated with methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms. The objective of the present study is to assess B9 vitamin supplementation associated with MTHRF C677T polymorphism can be effective on NCS variations in patients.

Materials And Methods: This study is a randomized, double-blind, placebo-controlled study. Patients were randomly allocated to either intervention (1 mg of folic acid, = 40) or placebo ( = 40) groups based on parallel group design. Blood samples were taken to determine the serum levels of folic acid and homocysteine. The NCS data were collected for the assessment of diabetic neuropathy. Genotyping was performed for C677T polymorphism of the MTHFR gene.

Results: Four months after intervention, patients significantly observed change of serum folic acid and homocysteine levels based on C677T genotypes in the MTHFR gene. The amplitude of sensory peroneal nerve between intervention and placebo groups with CC genotype was significantly different (2.8 ± 1.6 vs. 1.9 ± 1.1). However, peak latency and amplitude of sensory sural nerve between CC (3.8 ± 1.8 vs. 4.0 ± 1.5 for peak latency and 3.5 ± 1.0 vs. 2.5 ± 1.0 for amplitude; and CT + TT genotypes (3.7 ± 1.7 vs. 3.9 ± 1.3 for peak latency and 3.2 ± 1.0 vs. 2.3 ± 1.1 for amplitude) were significant. Furthermore, significant difference for variables of motor tibial nerve and motor peroneal nerve amplitude was observed in different groups of MTHFR C677T genotypes (5.4 ± 2.9 vs. 4.6 ± 3.2 for onset-latency of tibial nerve between CC genotype; 4.8 ± 2.8 vs. 4.6 ± 3.2 for onset-latency of tibial nerve between CT + TT genotype; 0.6 ± 0.2 vs. 0.3 ± 0.1 for amplitude of tibial nerve between CC genotype; 0.5 ± 0.3 vs. 0.3 ± 0.2 for amplitude of tibial nerve between CT + TT genotype; 26.0 ± 13.3 vs. 23.2 ± 13.4 for velocity of tibial nerve between CC genotype; 26.0 ± 13.7 vs. 23.1 ± 9.6 for velocity of tibial nerve between CT + TT genotype; 1.6 ± 1.0 vs. 0.9 ± 0.7 for amplitude of peroneal nerve between CC genotype; 1.4 ± 0.7 vs. 0.9 ± 0.5 for amplitude of peroneal nerve between CT + TT genotype).

Conclusion: The study determined that MTHFR C677T polymorphism effects the efficacy of folic acid supplementation on serum folic acid, homocysteine levels and some NCS parameters in diabetic polyneuropathy patients.
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http://dx.doi.org/10.4103/jrms.JRMS_774_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521607PMC
April 2019

Correlations between the expression of hTERT and α and β splice variants in human brain tumors.

Adv Clin Exp Med 2019 04;28(4):507-513

Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease and Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Iran.

Background: Astrocytomas are diffusible infiltrative and aggressive brain tumors that are extensive and heterogeneous clusters of neoplastic growths in the central nervous system (CNS). Meningioma tumors are commonly benign but may demonstrate an invasive pattern with frequent recurrences. Human telomerase reverse transcriptase (hTERT) is an unfavorable prognostic factor for several types of cancers, and there are controversies about its role.

Objectives: In the present study, we investigated the relative expression of hTERT splice variants in 2 groups of brain tumors compared to non-tumor samples.

Material And Methods: The mRNA of 40 brain tumor samples and 4 control samples was extracted; mRNA expression of hTERT α-deletion and β-deletion variants, as well as the wild type isoform, was quantified using quantitative reverse transcription polymerase chain reaction (RT-qPCR).

Results: The α-deletion variant was significantly expressed in primary benign meningeal tumors (p = 0.01). The results indicate a positive correlation between the relative expression of hTERT mRNA transcript and α-deletion and β-deletion variants in both groups of tumors (meningiomas and astrocytomas). A strong association between the expression of the full-length splice variant and the β-deletion variant was observed in astrocytoma tumors (p = 0.045). The most significant correlations were found between the hTERT full-length and β-deletion variants in high-grade meningiomas (p = 0.018, correlation coefficient (CC) = 0.964) and grade II astrocytomas (p = 0.015; CC = 0.580). In addition, in low grades of both types of tumors, the hTERT full-length variant and especially the α-deletion variant were the predominant isoforms. The overexpression of hTERT and β-deletion variants in high grades of these tumors was statistically significant. Our findings indicate that α-deletion and β-deletion isoforms are associated with high levels of full-length hTERT mRNA in both groups of brain tumor patients.

Conclusions: Changes in the splicing pattern of hTERT splice variants in brain tumors and their correlation with pathological alterations in cells could be applied as diagnostic or prognostic biomarkers, or possibly as targets for cancer therapy. However, the function and biological role of hTERT splice variants remain to be clarified.
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http://dx.doi.org/10.17219/acem/81934DOI Listing
April 2019

Variants in Human Prostacyclin Receptor Gene in Patients with Migraine Headache.

Iran J Psychiatry 2018 Oct;13(4):239-243

Psychiatry and Psychology Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Prostaglandin I2 receptor plays a major physiologic role in the relaxation of arterial smooth muscle and vasodilation and possibly during migraine attacks. Therefore, in this study, the coding and noncoding exons and exon-intron boundaries of Prostaglandin I2 receptor gene were examined in patients with migraine headache and healthy controls and the potential effects of identified single nucleotide variations were evaluated using direct PCR-sequencing and in silico analysis. In this study, the peripheral blood samples of 50 patients and 50 controls were examined to find any mutation in coding and noncoding exons and exon-intron boundaries of PTGIR gene. DNA was extracted and all the samples were amplified by polymerase chain reaction (PCR) and sequenced. In this study, the patients had a mean age of 35.235 ± 10.99 years (range, 9-60 yrs.), and female to male ratio was 4:1 in this group. The controls had a mean age of 35.058 ± 11.116 years (range, 8-59 yrs.), and female to male ratio was 3.7:1.3 in this group. Two patients had mutations in exon 2. The first mutation was located in exon 2 (at amino acid position 251) of PTGIR gene at nucleotide position c.866A > T, a synonymous variant described previously in the database. The second mutation was located in exon 2 c.867G > A, which is a missense variant. Sequence analysis revealed high occurrence of previously reported intronic variants mostly in a homozygous statue. The data supported the hypothesis that mutations in PTGIR gene, particularly the mutation we described, should be considered even in cases of migraine. The presence of this mutation in patients with family history raises important issues regarding genetic counselling.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320380PMC
October 2018

MDA-7/interleukin 24 (IL-24) in tumor gene therapy: application of tumor penetrating/homing peptides for improvement of the effects.

Expert Opin Biol Ther 2019 03 21;19(3):211-223. Epub 2019 Jan 21.

c Bacteriology and Virology Department, School of Medicine , Shiraz University of Medical Sciences , Shiraz , Iran.

Introduction: MDA-7/Interleukin-24 (IL-24), as a pleiotropic cytokine, exhibits a specific tumor suppression property that has attracted a great deal of attention. While its anti-tumor induction is mostly attributed to endogenous gene expression, attachment of secreted MDA-7/IL-24 to cognate receptors also triggers the death of cancerous cell via different pathways. Therefore, precise targeting of secreted MDA-7/IL-24 to tumor cells would render it more efficacy and specificity.

Areas Covered: In order to target soluble cytokines, particularly MDA-7/IL-24 to the neighbor tumor sites and enhance their therapeutic efficiency, fusing with cell penetrating peptides (CPPs) or Tumor homing peptides (THPs) seems logical due to the improvement of their bystander effects. Although the detailed anti-tumor mechanisms of endogenous mda-7/IL-24 have been largely investigated, the significance of the secreted form in these activities and methods of its improving by CPPs or THPs need more discussion.

Expert Opinion: While the employment of CPPs/THPs for the improvement of cytokine gene therapy is desirable, to create fusions of CPPs/THPs with MDA-7/IL-24, some hurdles are not avoidable. Regarding our expertise, herein, the importance of CPPs/THPs, needs for their elegant designing in a fusion structure, and their applications in cytokine gene therapy are discussed with a special focus on mda-7/IL-24.
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http://dx.doi.org/10.1080/14712598.2019.1566453DOI Listing
March 2019

TRPC6 Mutational Analysis in Iranian Children With Focal Segmental Glomerulosclerosis.

Iran J Kidney Dis 2018 Nov;12(6):341-349

Isfahan Kidney Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Introduction: Focal segmental glomerulosclerosis (FSGS) ranks among nephrotic syndromes. Research shows that FSGS is brought about by several genes including transient receptor potential cation channel subfamily c member 6 (TRPC6). This study aimed to investigate TRPC6 gene in Iranian FSGS children.

Materials And Methods: Twenty-six FSGS patients were included. They were all under 16 years old. Polymerase chain reaction amplification and sequencing were performed to examine exons 2 and 13 of TRPC6 gene.

Results: Sampling was performed when the patients had a mean age of 9.26 ± 3.19 years. Sixteen children were boys (61.5%); male-female ratio was 1.35:1. Four patients (15.4%) were diagnosed with TRPC6 variants. Three missense nonsynonymous mutations (C121S, D130V, and G162R) and 1 synonymous mutation (I111I) were detected. All variants were novel; in silico analysis predicted D130V and G162R as pathogenic. Patients with and without mutations were not different significantly regarding age at disease onset, sex, consanguinity, hypertension, hematuria, serum creatinine and albumin, rate of progression to kidney failure, response to steroids, and resistance to cyclosporine A and cyclophosphamide.

Conclusions: This study examined exons 2 and 13 of TRPC6 gene in Iranian FSGS children. Four novel TRPC6 variants were detected; in silico analysis showed that 2 variants (D130V and G162R) could be pathogenic. It could be concluded that TRPC6 may be useful for genetic screening in Iranian FSGS children.
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November 2018

In silico analysis of SLC3A1 and SLC7A9 mutations in Iranian patients with Cystinuria.

Mol Biol Rep 2018 Oct 1;45(5):1165-1173. Epub 2018 Aug 1.

Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, P.O.Box: 81746-73461, Isfahan, Iran.

Cystinuria is an autosomal recessive defect in reabsorptive transport of cystine and the dibasic amino acids ornithine, arginine, and lysine from renal tubule and small intestine. Mutations in two genes: SLC3A1, encoding the heavy chain rbAT of the renal cystine transport system and SLC7A9, the gene of its light chain b AT have a crucial role in the diseases. In our previous studies from Iranian populations with Cystinuria totally six and eleven novel mutations respectively identified in SLC3A1 and SLC7A9 genes. In this study, we conducted an in silico functional analysis to explore the possible association between these genetic mutations and Cystinuria. MutationTaster, PolyPhen-2, PANTHER, FATHMM. PhDSNP and MutPred was applied to predict the degree of pathogenicity for the missense mutations. Furthermore, Residue Interaction Network (RIN) and Intron variant analyses was performed using Cytoscape and Human Slicing Finder softwares. These genetic variants can provide a better understanding of genotype-phenotype relationships in patients with Cystinuria. In the future, the findings may also facilitate the development of new molecular diagnostic markers for the diseases.
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http://dx.doi.org/10.1007/s11033-018-4269-6DOI Listing
October 2018

Meta-Analysis of the Association between GABA Receptor Polymorphisms and Autism Spectrum Disorder (ASD).

J Mol Neurosci 2018 May 3;65(1):1-9. Epub 2018 May 3.

Mohkam-kar Health Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Previous studies have reported the association of GABA receptor subunits B3, A5, and G3 single-nucleotide polymorphisms (SNPs) in chromosome 15q11-q13 with autism spectrum disorders (ASDs). However, the currently available results are inconsistent. This study aimed to investigate the association between ASD and the GABA receptor SNPs in chromosomal region 15q11-q13. The association was calculated by the overall odds ratio (OR) with a 95% confidence interval (CI). We used sensitivity analyses and the assessment of publication bias in our meta-analysis. Eight independent case-control studies involving 1408 cases and 2846 healthy controls were analyzed, namely, 8 studies for GABRB3 SNPs as well as 4 studies for GABRA5 and GABRG3 polymorphisms. The meta-analysis showed that GABRB3 polymorphisms in general are not significantly associated with autism [OR = 0.846 (95% CI): 0.595-1.201, I = 79.1%]. Further analysis indicated that no associations were found between GABRB3 SNPs and autism on rs2081648 [OR = 0.84 (95% CI) = 0.41-1.72, I = 89.2%] and rs1426217 [OR = 1.13 (95% CI) = 0.64-2.0, I = 83%]. An OR of 0.95 (95% CI) = 0.77-1.17 was reported (I = 0.0%) for GABRA5 SNPs and an OR of 0.96 (95% CI) = 0.24-3.81 was obtained from GABRG3 SNPs (I = 97.8%). This meta-analysis provides strong evidence that different SNPs of GABA receptor B3, A5, and G3 subunit genes located on chromosome 15q11-q13 are not associated with the development of autism spectrum diseases in different ethnic populations. However, in future research, large-scale and high-quality studies are necessary to confirm the results.
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http://dx.doi.org/10.1007/s12031-018-1073-7DOI Listing
May 2018

Novel Variants and Copy Number Variation in CDH1 Gene in Iranian Patients with Sporadic Diffuse Gastric Cancer.

J Gastrointest Cancer 2019 Sep;50(3):420-427

Department of Pathology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Introduction: The aim of this study was to survey the nucleotide changes and copy number variations (CNV) in the CDH1 gene in Iranian patients with sporadic diffuse gastric cancer (SDGC).

Materials And Methods: In this study, 28 patients were examined who upon gastrectomy had been diagnosed with SDGC according to the familial history and histopathological criteria which was confirmed by the pathologist. DNA extraction was performed from formalin-fixed paraffin-embedded tissues using a phenol-chloroform method following xylene deparaffinization. Determination of DNA sequence by Sanger was performed using PCR amplification of 16 exons and boundaries of intron/exon of CDH1 gene. Multiplex ligation-dependent probe amplification (MLPA) was performed on patients with pathogenic disorders in the sequence.

Results: In total, patients included 20 males and 8 females. Of all patients, 12 patients were under 45 years old (early onset gastric cancer, EODC) and 16 patients were older. The tumor was diagnosed in the early TNM stage (I, II) in six patients and in late stages (III, IV) in 19 cases. Altogether, 16 variants (three exonic with one new variant and 13 intronic with nine new variants) were found in DNA sequencing of the CDH1 gene in five samples. Also, using MLPA, a new duplication in exon 9 and one deletion in exon 2 were detected in two other patients. Altogether, CDH1 variants were identified in seven out of 28 patients (25%).

Conclusion: Our study revealed several novel somatic variants in the CDH1 gene in Iranian patients with sporadic diffuse GC. Our data supports the hypothesis that mutations in CDH1 gene, and particularly the mutations we describe, should be considered, even in sporadic cases of gastric cancer. The presence of these mutations in patients raises important issues regarding genetic counseling and diagnostic test in DGC patients.
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http://dx.doi.org/10.1007/s12029-018-0082-7DOI Listing
September 2019

Evaluation of miR-362 Expression in Astrocytoma of Human Brain Tumors.

Adv Biomed Res 2017 16;6:129. Epub 2017 Oct 16.

Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-communicable Disease, Isfahan, Iran.

Background: Patients affected by gliomas have a poor prognosis. Astrocytoma is a subtype of glioma. Identification of biomarkers could be an effective way to an early diagnosis of tumor or to distinguish more aggressive tumors that need more intensive therapy. In this study, we investigated whether the expression of miR-362 was increased or decreased in patients with different grades of astrocytoma.

Materials And Methods: miR-362 expression was compared in 25 patients with astrocytoma with that of 4 normal nonneoplastic brain tissues.

Results: In all tumor tissues, the expression of miR-362 was significantly decreased relative to its expression in normal brain tissues. However, there was no significant difference between miR-362 expressions in high and low grades of astrocytoma.

Conclusions: In conclusion, miR-362 showed a down-regulation pattern in astrocytoma tissues that was different from the pattern obtained from previously published microarray studies.
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http://dx.doi.org/10.4103/2277-9175.216782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5672651PMC
October 2017

A Report of a Novel Mutation in Human Prostacyclin Receptor Gene in Patients Affected with Migraine.

Iran J Psychiatry 2017 Jul;12(3):219-222

Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-Communicable Diseases, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran; Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

The human prostacyclin receptor gene encodes the human prostacyclin receptor, which is a part of the vasodilator system, during migraine attacks and almost certainly plays an important role in the mechanism of this disease. The present study aimed at determining any variants in PTGIR gene by means of PCR and direct sequencing. Blood samples were taken from the patients, and genomic DNA was extracted. Polymerase chain reaction was performed on the extracted DNA. The PCR products were then sequenced using the Sanger method. When reviewing the familial and clinicopathological history of the 2 patients, we found that both had symptoms of migraine with visual aura and that their mothers were also suffering from migraine. Their parents were not relatives prior to marriage. Direct sequencing of Exon 2 of the PTGIR gene showed the presence of 2 mutations. These mutations were heterozygous and made the following changes: g.1626T>A, c.754T>A, cDNA.867T>A, and p.S252T for the first mutation, and c.753C>T, cDNA866C>T, g.1625C>T, and p.C251C for the second mutation. The first mutation altered the amino acid and was a novel mutation. The second change was a conservative mutation that has already been reported. The prediction results of silico studies indicated that the c.754T>A change would negatively affect the protein's function and seemed to cause the disease. However, functional analysis is required to confirm the association between the variant and the disease.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5640585PMC
July 2017

MeDIP Real-Time qPCR has the Potential for Noninvasive Prenatal Screening of Fetal Trisomy 21.

Int J Mol Cell Med 2017 15;6(1):13-21. Epub 2017 Feb 15.

Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Noncommuni-cable Disease, Isfahan University of Medical Sciences, Isfahan, Iran.

This study aimed to verify the reliability of the 7 tissue differentially methylated regions used in the methylated DNA immunoprecipitation (MeDIP) real- time quantitative polymerase chain reaction (real-time qPCR) based approach of fetal DNA in maternal blood to diagnosis of fetal trisomy 21. Forty pregnant women with high risk pregnancy who were referred after first or second trimester screening tests, were selected randomly. For each sample whole DNA extraction (mother and fetus), fragmentation of DNA, immunoprecipitation of methylated DNA and real- time qPCR using 7 primer pairs was performed. D-value for each sample was calculated using the following formula D = -4.908+ 0.254 X+ 0.409 X+ 0.793 X+ 0.324 X+ 0.505 X+ 0.508 X+ 0.691 X. In all normal cases, D value was negative, while it was positive in all trisomy cases. Therefore, all normal and trisomy 21 cases were classified correctly which correspond to 100% specificity and 100% sensitivity for this method. The MeDIP real-time qPCR method has provided the opportunity for noninvasive prenatal diagnosis of fetal trisomy 21 to be potentially employed into the routine practice of diagnostic laboratories.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5568188PMC
February 2017

Assessment Effects of Resveratrol on Human Telomerase Reverse Transcriptase Messenger Ribonucleic Acid Transcript in Human Glioblastoma.

Adv Biomed Res 2017 27;6:73. Epub 2017 Jun 27.

Stem Cell Biology Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Background: Glioblastoma (GBM) is the most common and aggressive brain tumor, which has a poor prognosis despite the advent of different therapeutic strategies. There are numerous molecular biomarkers to contribute diagnosis, prognosis, and prediction of response to the current therapy in GBM. One of the most important markers that are potentially valuable is immortalization-specific or immortalization-associated marker named "hTERT messenger ribonucleic acid (mRNA)" the key subunit of telomerase enzyme, which is expressed in more than 85% of cancer cells, in spite of the majority of normal somatic cells. In this study, we investigated the effects of resveratrol (RSV) on this mRNA marker level, leading to cancer progression.

Materials And Methods: U-87MG cell line was obtained from Pasteur Institute of Iran and treated with various concentrations of 0-160 μg/mL of RSV and at different time points (24, 48, and 72 h). To evaluate viability of U-87MG cells, standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed. Real-time polymerase chain reaction (RT-PCR) was used for comparative and quantitative assessment of human telomerase reverse transcriptase (hTERT) mRNA copy number versus control-untreated group.

Results: The results of our investigation suggested that RSV effectively inhibited cell growth and caused cell death in dose-dependent ( < 0.05) and not in time-dependent manner ( > 0.05), . Interestingly, quantitative RT-PCR analysis demonstrated that at half inhibition concentration, RSV dramatically decreased mRNA expression of hTERT, the catalytic subunit of telomerase enzyme, which leads to prevention of cell division and tumor progression.

Conclusion: With regard to downregulation of this immortalization-associated marker, RSV may potentially be used as a therapeutic agent against GBM.
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http://dx.doi.org/10.4103/2277-9175.209047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5501037PMC
June 2017

Identification of B and T cell epitope based peptide vaccine from IGF-1 receptor in breast cancer.

J Mol Graph Model 2017 08 8;75:316-321. Epub 2017 Jun 8.

Department of Genetics and Molecular Biology, School of Medicine, Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran. Electronic address:

The insulin-like growth factor-1 receptor (IGF-1R) plays a key role in proliferation, growth, differentiation, and development of several human malignancies including breast and pancreatic adenocarcinoma. IGF-1R targeted immunotherapeutic approaches are particularly attractive, as they may potentially elicit even stronger antitumor responses than traditional targeted approaches. Cancer peptide vaccines can produce immunologic responses against cancer cells by triggering helper T cell (Th) or cytotoxic T cells (CTL) in association with Major Histocompatibility Complex (MHC) class I or II molecules on the cell surface of antigen presenting cells. In our previous study, we set a technique based on molecular docking in order to find the best MHC class I and II binder peptides using GOLD. In the present work, molecular docking analyses on a library consisting of 30 peptides mimicking discontinuous epitopes from IGF-1R extracellular domain identified peptides 249 and 86, as the best MHC binder peptides to both MHC class I and II molecules. The receptors most often targeted by peptide 249 are HLA-DR4, HLA-DR3 and HLA-DR2 and those most often targeted by peptide 86 are HLA-DR4, HLA-DP2 and HLA-DR3. These findings, based on bioinformatics analyses, can be conducted in further experimental analyses in cancer therapy and vaccine design.
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http://dx.doi.org/10.1016/j.jmgm.2017.06.004DOI Listing
August 2017

Report of /rBAT gene mutations in Iranian cystinuria patients: A direct sequencing study.

J Res Med Sci 2017 15;22:33. Epub 2017 Mar 15.

Department of Urology, Urology and Kidney Transplantation Research Center, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: Considering a few studies on the genetic basis of the cystinuria in the Middle East and the population-specific distribution of mutations in the , we tried to find genetic variants in three exons (1, 3, and 8) of .

Materials And Methods: In this study, exons 1, 3, and 8 of gene of 25 unrelated cystinuria patients searched for genetic variations by polymerase chain reaction and sequencing.

Results: There were five different variations in our studied population. We found one mutation in the gene including missense variant M467K and identified three polymorphisms: nonsynonymous variant G38G, c. 610 + 169C>T and c. 610 + 147C>G within the gene, and one new variant.

Conclusion: Our results confirm that cystinuria is a heterogeneous disorder at the molecular level and more studies are needed to identify the distribution and frequency of mutations causing cystinuria in the Iranian population.
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http://dx.doi.org/10.4103/1735-1995.202149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5390536PMC
March 2017

Comparison of the Frequency of Y-short Tandem Repeats Markers between Sadat and Non-Sadat Populations in Isfahan Province of Iran.

Adv Biomed Res 2017 7;6:33. Epub 2017 Mar 7.

Department of Genetics and Molecular Biology, Research Institute for Primordial Prevention of Noncommunicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran; Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Noncommunicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: Y chromosome is one of the two sex chromosomes and is male specific. Due to limited genetic exchange, the main part of that is passed virtually unchanged from one generation to next generation. The short tandem repeats (STRs) are almost constant on chromosomes that make them as an appropriate factor for use in population genetic studies. In this study, we used the STRs of Y chromosome markers in Sadat families and comparison with other families was investigated.

Materials And Methods: In this study, sampling was done from fifty unrelated males of Sadat families and fifty unrelated males of non-Sadat families. After the extraction of DNA from blood samples and primer design, polymerase chain reaction (PCR) was performed for each primer pairs separately. The PCR products were run on agarose gel that followed by running on polyacrylamide gel for better resolution. In addition, some sequenced samples were used as identified markers to determine the length of other alleles in polyacrylamide gel.

Results: The survey of six STR in two case and control groups was carried out, and analysis revealed that the frequency of some alleles is different in case group compared to control group. Allele frequency of the markers DYS392, DYS393, DYS19, DYS390, DYS388, and DYS437 on the Y chromosome in Sadat families was quite different in comparison with other families.

Conclusions: The reason for these differences in allele frequencies of the Sadat family in comparison with other families is having a common ancestor.
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http://dx.doi.org/10.4103/2277-9175.188493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360006PMC
March 2017

Simple and Easy to Perform Preimplantation Genetic Diagnosis for β-thalassemia Major Using Combination of Conventional and Fluorescent Polymerase Chain Reaction.

Adv Biomed Res 2017 7;6:23. Epub 2017 Mar 7.

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

Background: Thalassemias are the most common monogenic disorders in many countries throughout the world. The best practice to control the prevalence of the disease is prenatal diagnosis (PND) services. Extensive practicing of PND proved effective in reducing new cases but on the other side of this success high abortion rate is hided, which ethically unfair and for many couples, especially with a previous experience of a therapeutic abortion, or moral concerns, is not a suitable choice. Preimplantation genetic diagnosis (PGD) is a strong alternative to conventional PND. At present PGD is the only abortion free fetal diagnostic process. Considering the fact that there are more than 6000 single gene disorders affecting approximately 1 in 300 live-births, the medical need for PGD services is significant.

Materials And Methods: In the present study development of a PGD protocol for a thalassemia trait couple using nested multiplex fluorescent polymerase chain reaction (PCR) for the combination of polymorphic linked short tandem repeat (STR) markers and thalassemia mutations is described. Restriction fragment length polymorphism used to discriminate between wild and mutated alleles.

Results: In PGD clinical cycle, paternal and maternal alleles for D11S988 and D11S1338 STR markers were segregated as it was expected. PCR product for IVSII-1 mutation was subsequently digested with BtscI restriction enzyme to differentiate normal allele from the mutant allele. The mother's mutation, being a comparatively large deletion, was detectable through size differences on agarose gel.

Conclusion: The optimized single cell protocol developed and evaluated in this study is a feasible approach for preimplantation diagnosis of β-thalassemia in our patients.
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http://dx.doi.org/10.4103/2277-9175.201682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360017PMC
March 2017

A Novel Mutation in SLC7A9 Gene in Cystinuria.

Iran J Kidney Dis 2017 Mar;11(2):138-141

Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-communicable Disease and Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Introduction: Cystinuria is an inherited disorder affecting luminal transport of cystine and dibasic amino acids. Because of the poor solubility of cystine in urine, stone formation in the kidney occurs frequently. Cystinuria is associated with mutations in the SLC3A1 and SLC7A9 genes. Despite the population-specific distribution of mutations in the SLC7A9 genes, there are few genetic data reported for cystinuric patients from the Middle East.

Materials And Methods: Exon 4 of the SLC7A9 gene was sequenced in 21 patients with cystinuria, using the polymerase chain reaction and sequencing methods.

Results: A new variation in exon 4 of the SLC7A9 gene was identified, which was insertion of 1 adenine nucleotide between 2 cytosine nucleotides in position c.213-214insA.

Conclusions: It seems to be important since it causes frame shift and it may be an important cause to make disease.
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March 2017

Effect of teicoplanin on the expression of c-myc and c-fos proto-oncogenes in MCF-7 breast cancer cell line.

Adv Biomed Res 2016 28;5:172. Epub 2016 Nov 28.

Department of Genetics and Molecular Biology, Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Noncommunicable Disease, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: Teicoplanin is a member of vancomycin-ristocetin family of glycopeptide antibiotics. It mediated wound healing by increasing neovascularization possibly through activation of MAP kinase signaling pathway. The aim of this study is an evaluation of c-myc and c-fos genes expression after treatment of cells by teicoplanin and determines whether this glycopeptide antibiotic exerts its proliferation effects by influencing the expression of these genes. Hence, this study was designed to elucidate one possible mechanism underlying teicoplanin effects on cell proliferation using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay.

Materials And Methods: Breast cancer cell line, MCF-7, was cultured, and three different concentrations of teicoplanin were added to the plates. We measured the cell proliferation rate by MTT assay. After cell harvesting, total RNA was extracted to synthesize single-stranded cDNA. Real-time polymerase chain reaction was performed, and the data were analyzed.

Results: It was observed that the level of c-fos and c-myc genes' expressions was decreased at all three different concentrations of teicoplanin.

Conclusion: it could be concluded that although teicoplanin is considered as an enhancing cell growth and proliferation, but probably its effect is not through MAP kinase signaling pathway or perhaps even has inhibitory effect on the expression of some genes such as c-myc and c-fos in this pathway. Hence, the mechanism of action of teicoplanin for increasing cell propagation, through cell signaling pathways or chromosomal abnormalities, remains unclear, and further studies should be conducted.
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http://dx.doi.org/10.4103/2277-9175.190984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5156965PMC
November 2016

Down Syndrome: Current Status, Challenges and Future Perspectives.

Int J Mol Cell Med 2016 10;5(3):125-133. Epub 2016 Aug 10.

Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.; Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran.

Down syndrome (DS) is a birth defect with huge medical and social costs, caused by trisomy of whole or part of chromosome 21. It is the most prevalent genetic disease worldwide and the common genetic cause of intellectual disabilities appearing in about 1 in 400-1500 newborns. Although the syndrome had been described thousands of years before, it was named after John Langdon Down who described its clinical description in 1866. Scientists have identified candidate genes that are involved in the formation of specific DS features. These advances in turn may help to develop targeted therapy for persons with trisomy 21. Screening for DS is an important part of routine prenatal care. Until recently, noninvasive screening for aneuploidy depends on the measurement of maternal serum analytes and ultrasonography. More recent progress has resulted in the development of noninvasive prenatal screening (NIPS) test using cell-free fetal DNA sequences isolated from a maternal blood sample. A review on those achievements is discussed.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125364PMC
August 2016