Association of rs16917496 polymorphism at the miR-502 binding site in the SET8 3'UTR with the risk of Prostate Cancer and benign prostatic hyperplasia

Background: MicroRNAs (miRNAs) can bind to the 3'-untranslated regions (UTRs) of messenger RNAs, where they interfere with translation and thereby regulate cell differentiation, apoptosis, and tumorigenesis. Genetic polymorphisms in the 3'-UTRs targeted by miRNAs alter the strength of miRNA binding in a manner that affects the behavior of individual miRNAs. The histone methyltransferase SET8 has been reported to be a regulator of Tumor Protein 53 (TP53) methylation, a tumor suppressor gene, and regulate genomic stability. Furthermore, an association between the TP53 and Prostate Cancer has been reported in several studies. The present study aimed to evaluate whether (rs16917496) polymorphism at the miR-502 binding site in the 3' untranslated region of the histone methyltransferase SET8 is associated with the expression of this gene in Benign Prostatic Hyperplasia (BPH) and prostate cancer (PCa) patients.Materials and Methods: We examined whether an rs16917496 polymorphism is associated with the risk of PCa and BPH in the Iranian population. This case-control study included 40 patients with pathologically confirmed PCa, 59 patients with BPH, and 45 controls. The rs16917496 polymorphism was determined using a restriction fragment length polymorphism (RFLP).Results: We found significant association of rs16917496 in benign prostatic hyperplasia (BPH). The most frequent genotype in the control, prostate cancer, and BPH groups were TT, TC, and CC, respectively.Conclusion: This study demonstrates that the heterozygote genotype of the SET8 polymorphism in the mir-502 gene could be considered a risk factor for the emergence of prostate cancer

Characterization of a de novo constitutional balanced translocation

Abstract Reciprocal balanced translocations associated with clinical features are very rare. This study reports cytogenetic and molecular cytogenetic findings in a 3-year-old patient with mild developmental retardation, slight hypotone with a de novo balanced 46, XX, t(2; 11) (q33; q23) translocation. G-banded chromosomes and FISH-Analysis were used to examine the patient's karyotype as well as her parents'. FISH-probes prepared with specific RP11-BAC clones mapped near 2q33 and 11q23 regions were used to characterize the location of the breakpoints. The FISH results revealed that one of the break points is located within the human NBEAL1-Gene locus on chromosome 2, suggesting a correlation between this gene disruption and the patient’s mild developmental retardation. 

Understanding the Molecular Basis of Fragile X Syndrome Using Differentiated Mesenchymal Stem Cells

Abstract Objectives Fragile X syndrome (FXS) has been known as the most common cause of inherited intellectual disability and autism. This disease results from the loss of fragile X mental retardation protein expression due to the expansion of CGG repeats located on the 5’ untranslated region of the fragile X mental retardation 1 (FMR1) gene. Materials & Methods In the present study, the peripheral blood-mesenchymal stem cells (PB-MSCs) of two female full mutation carriers were differentiated into neuronal cells by the suppression of bone morphogenesis pathwaysignaling. Then, the expression of genes adjacent to CGG repeats expansion, including SLIT and NTRK-like protein 2 (SLITRK2), SLIT and NTRK-like protein 4 (SLITRK4), methyl CpG binding protein 2 (MECP2), and gamma-aminobutyric acid receptor subunit alpha-3 (GABRA3), were evaluated in these cells using SYBR Green real-time polymerase chain reaction. Results The obtained results indicated that the expression of SLITRK2 and SLITRK4 were upregulated and downregulated in the neuron-like cells differentiated from the PB-MSCs of females with FMR1 full mutation, compared to that of the normal females, respectively. Furthermore, the expression of MECP2 and GABRA3 genes were observed to be related to the phenotypic differences observed in the female FMR1full mutation carriers Conclusion The observed association of expression of genes located upstream of the FMR1 gene with phenotypic differences in the female carriers could increase the understanding of novel therapeutic targets for patients with mild symptoms of FXS and the patients affected by other FMR1-related disorder

What we Know so far about Myxovirus Resistance Protein A (MxA) as a Biomarker of Interferon-Beta Therapy in Patients with Multiple Sclerosis: a Systematic Review

Introduction: Multiple sclerosis (MS) is one of the most common neurological disabling diseases in human societies with no complete cure. IFN-β has been proven to be an important advance in the MS treatment, but early identification of treatment failure is its major concern. Some researches revealed that MxA is an appropriate biomarker for predicting response to IFN-β, so we performed this study to evaluate the relationship between MxA level and response to INF- β treatment.Methods: International and internal databases were searched using “MxA”, “Myxovirus resistance protein A”, “IFN-β”, “interferon Beta”, “multiple sclerosis” and “MS keywords until October 2019. Inclusion criteria were original studies considering the MxA assays in MS patients under IFN-β therapy. Some reported cut-offs from partially the same settings (7 studies) were pooled using the weighted average. Finally, the overall statements of the included studies were compared and discussed to obtain a comprehensive conclusion about the clinical value of MxA assays in patient monitoring and designing their treatment plan. Results: A total of 456 articles were identified. The Screening was led to exclusion of 427 articles. Finally, 28 original studies met the inclusion criteria for this systematic review. Almost all studies have concluded that the MxA is significantly correlated with response to IFN-β therapy and also MxA expression is under the direct effect of Neutralizing antibody (NAb) against IFN-β. Reported cut-offs for MxA ranged from 3.3 to 6.3 NR and the weighted average of them was estimated to be 4.1 NR. Conclusion: It could be suggested that in patients under IFN-β therapy with an active disease which doesn’t fulfill the criteria for the breakthrough disease, MxA level can help to determine whether to continue the drug and follow up a patient or change the treatment regimen

The Genetic Causes of Male Infertility in Iranian Population; A systematic Review

Introduction: Infertility affects an estimated 15% of couples globally and in Iran, a quarter of couples experiences primary infertility. Males are found to be individually responsible for 20-30% of infertility cases and contribute to 50% of cases totally. When assisted reproductive technologies (ARTs) are used to acquire pregnancy, a sufficient (epi) genetic diagnosis of male infertility (MI) is of main matter to consider if a genetic abnormality will be transmit-ted to offspring. Infertility centers together with Infertility research centers had been founded since 1994 in Iran and many articles from research projects have been published.Materials and Methods: This literature investigated the possible genetic causes mechanisms underlying Iranian male infertility by extensive article searches.  First, we reviewed available data from the Google Scholar, PubMed, Scopus, Web of Science, IranMedex, MEDLIB, IranDoc and Scientific Information Database were searched for articles published until 2018, using the MeSH terms for a variety of chromosome abnormalities, Y-chromosome microdeletions, gene mutations, expression and polymorphisms, Male infertility and/or Iranian, regional and international population, to provides the evidence- based and a comprehensive, up-to- date evaluation of the multifactorial factors involved in Iranian infertile men.  Results: According to the strategy adopted initially, 274 manuscripts were found. After reviewing the titles, abstracts and manuscripts entirely cited, the total of 139 articles were obtained and selected according to the eligibility criteria. The 139 studies were divided into four predetermined categories that mentioned above.  Studies have good methodological validity. The sample is quite heterogeneous, given the very different design of the studies.Conclusion: MI is a complex, multi-factorial disease and the underlying reasons frequently remain unknown. It seems that the first line of genetic diagnosis in Iranian male infertility is similar to Global One. In all investigations conducted in Iran, there are vacancies in studies such as epigenetic modification studies, RNA (lncRNA, miRNA and piRNA) abnormalities, mutation detection and polymorphism studies in other genes involved in the spermatogenesis process. At present, we have a little information for some polymorphisms (MTHFR, GST, ER, and DAZL) and mutations (mtDNA, CATSPER) which require more extensive studies. Such articles help to find a better insight into the causes of infertility in the Iranian men's community and will provide valuable visions into the development of targeted personalized treatments for patients and the ascertainment of the reasons of idiopathic infertility.

Bioinformatics prioritization of SNPs perturbing microRNA regulation of hematological malignancy-implicated genes.

The contribution of microRNAs (miRNAs) to cancer has been extensively investigated and it became obvious that a strict regulation of miRNA-mRNA regulatory network is crucial for safeguarding cell health. Apart from the direct impact of miRNA dysregulation in cancer pathogenesis, genetic variations in miRNAs are likely to disrupt miRNA-target interaction. Indeed, many evidences suggested that SNPs within miRNA regulome are associated with the development of different hematological malignancies. However, a full catalog of SNPs within miRNAs target sites of genes relevant to hematopoiesis and hematological malignancies is still lacking. Accordingly, we aimed to systematically identify and characterize such SNPs and provide a prioritized list of most potentially disrupting SNPs. Although in the present study we did not address the functional significance of these potential disturbing variants, we believe that our compiled results will be valuable for researchers interested in determining the role of target-SNPs in the development of hematological malignancies

Association of catechol-o-methyl transferase gene polymorphism with prostate cancer and benign prostatic hyperplasia

Abstract BACKGROUND: A single nucleotide variation within catechol-o-methyl transferase (COMT) gene may alter the COMT enzyme activity level. Polymorphism of Val158Met in the COMT gene has been related to malignancy. In this regard, a study was carried out to find a possible association between the COMT gene polymorphism in patients with sporadic prostate cancer (PCa) and benign prostatic hyperplasia (BPH)

Performance and Predictive Value of First Trimester Screening Markers for Down Syndrome in Iranian Pregnancies

Objective: To investigate the performance of first trimester Down syndrome (DS) screening markers in Iranian pregnancies.Although sonographic and serum markers are currently recommended for the first trimester screening of Down syndrome, the screening performance of the markers depends on the race and ethnicity. Materials and methods: A retrospective case-control study using first trimester screening results recorded with the prenatal diagnostic multi-centers in Iran. A total of 6,384 pregnant women were examined from March 2012 to February 2017. Totally 100 Down syndrome cases and 266 matched controls were selected and the maternal characteristics, sonographic and biochemical screening data were collected. Statistical analysis was performed using logistic regression and descriptive statistics. A decision tree model was designed using the chi-squared automatic interaction detection method based on serum markers. Results: For screening of DS pregnancies, PAPP-A (cut-off 0.795 MoM) yielded the highest sensitivity (86%) and NB marker presented highest specificity (96.24%). combination of the biochemical markers PAPP-A and β-hCG (cut-off: 1.55 MoM) showed the highest sensitivity over other combined markers. The decision-tree model based on serum markers improved (91% DR For a 5% FPR) first trimester screening performance. Conclusion: The novel decision-tree model base on serum markers revealed a better predictive value to achieve high sensitivity and specificity of first trimester Down syndrome screening in Iranian population

Short communication Androgen receptor gene trinucleotide repeats as a marker for tracing disease in a family with intersex patients

Mutations of the androgen receptor (AR) gene giverise to a wide array of phenotypic abnormalities. Various mutations of the AR gene and expanded polyglutamine repeats (CAG) at exon 1 of the gene have been reported in patients with infertility and neurodegenerative diseases. However, the role of the AR gene trinucleotides repeats has not been systemically studied in those with hypospadias or genital ambiguity. In this study it was tried to find out the potential association between these repeats and sexual development in a family consisted of 10 persons including one girl with primary amenorrhea and two boys with severe hypospadias. Mother was heterozygote for both CAG and GGN repeats. All affected children inherited the longer CAG and GGN repeat from their mother and all their healthy siblings inherited shorter CAG and GGN repeat. Only one girl had heterozygous situation like her mother. Our results indicated that disease locus is in linkage disequilibrium with the CAG and GGN trinucleotide repeats in the AR gene

Mutation detection in human estrogen receptor βb gene in infertile male patients by denaturing high-performance liquid chromatography

Background: For screening sequence variations in genes, rapid turnover time is of fundamental importance. While, many of the current methods are unfortunately time consuming and technically difficult to implement. Denaturing high-performance liquid chromatography (DHPLC) method had been shown to be a high-throughput, time saving, and economical tool for mutation screening. Objective: In the present study DHPLC method was used to explore the potential association between estrogen receptor β gene (ESR2) variants and male infertility. Materials and Methods: DNA from 96 men with infertility and 96 normal male as control were screened for mutation in the nine exons of the ESR2 gene, using WAVE® DHPLC device equipped with a DNA separation column and automated sequence analysis on the ABI Prism 310. Results: DHPLC evaluation of ESR2 gene in 96 infertile patients, revealed one heterozygous sequence variation (IVS 8–4G>A) near the 5' splicing region of intron 8 in 5 patients. No variation was identified in control population. Conclusion: Mutation detection by DHPLC, as it is presented in this context, is a high-throughput, quick, and economical tool for mutation screening. The gene alterations in ESR2 gene that we've found might increase susceptibility to infertility; but without cDNA screening, the consequences of these genetic alterations cannot be predicted