Association of TNF-related apoptosis inducing ligand receptor (TRAIL-R) gene polymorphisms in Iranian Azeri patients with multiple sclerosis

Introduction: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system with various degrees of axonal damage. The TNF-related apoptosis inducing ligand receptor (TRAIL-R) might be playing an important role in the pathogenesis of MS. The objective of our study was to evaluate the association of two common polymorphisms is located in the TRAIL-R1 and TRAIL-R2 gene, in the pathogenesis of MS.Methods: We genotyped two single nucleotide polymorphisms in particular regions with single strand conformation polymorphism (SSCP) and Results obtained from the sequence of some samples, were analyzed using DNAMAN software. DNA was extracted from whole blood using the salting-out procedure. The distribution of genotype frequencies was analyzed using Pearson’s x2 test. Statistical significance was defined as p < 0.05.Results: No Significant differences in SNP rs4872077 were found between the PRMS and PPMS groups and No association was found between the genotype status of the rs1001793 and rs4872077 polymorphisms and the age at onset, disease duration, EDSS.Conclusion: Our study suggests no association between TRAILR polymorphisms and MS Disease. Nevertheless, this polymorphisms does not appear to be a severity marker of the disease, neither modifying the clinical progression of MS nor its therapeutic response

CHD2 haploinsufficiency is associated with developmental delay, intellectual disability, epilepsy and neurobehavioural problems

BACKGROUND: The chromodomain helicase DNA binding domain (CHD) proteins modulate gene expression via their ability to remodel chromatin structure and influence histone acetylation. Recent studies have shown that CHD2 protein plays a critical role in embryonic development, tumor suppression and survival. Like other genes encoding members of the CHD family, pathogenic mutations in the CHD2 gene are expected to be implicated in human disease. In fact, there is emerging evidence suggesting that CHD2 might contribute to a broad spectrum of neurodevelopmental disorders. Despite growing evidence, a description of the full phenotypic spectrum of this condition is lacking. METHODS: We conducted a multicentre study to identify and characterise the clinical features associated with haploinsufficiency of CHD2. Patients with deletions of this gene were identified from among broadly ascertained clinical cohorts undergoing genomic microarray analysis for developmental delay, congenital anomalies and/or autism spectrum disorder. RESULTS: Detailed clinical assessments by clinical geneticists showed recurrent clinical symptoms, including developmental delay, intellectual disability, epilepsy, behavioural problems and autism-like features without characteristic facial gestalt or brain malformations observed on magnetic resonance imaging scans. Parental analysis showed that the deletions affecting CHD2 were de novo in all four patients, and analysis of high-resolution microarray data derived from 26,826 unaffected controls showed no deletions of this gene. CONCLUSIONS: The results of this study, in addition to our review of the literature, support a causative role of CHD2 haploinsufficiency in developmental delay, intellectual disability, epilepsy and behavioural problems, with phenotypic variability between individuals

Evaluating the mediating role of cognitive emotion regulation strategies in the relationship between body shame and body deformity disorder symptoms

Background and purpose: Body dysmorphia disorder is a psychiatric disorder that is characterized by an excessive concern about a slight defect or defect in physical appearance that leads to dysfunction in one or more areas of the body. This research was conducted with the aim of evaluating the mediating role of cognitive emotion regulation strategies in the relationship between body shame and body deformity disorder symptoms. Methods: The method of this research is structural equation modeling. The statistical population of this research includes women and girls referring to the beauty clinics of the 4th and 8th districts of Tehran, of which there are 232 people and the sampling method in this research is sampling. The main tool for collecting information in this research is to measure self-objectification, the body monitoring subscale, and to measure body shame, the body shame subscale is from the objectified body awareness scale of McKinley and Hyde (1996), the Cognitive Emotion Regulation Questionnaire by Garnefski, Kraaij, & Spinhoven (2001) and the body deformity questionnaire used by Stozin et al. (1998). In order to determine the presence or absence of influence between the variables and estimate and generalize the results obtained from the sample size to the statistical population, correlation model, Pearson correlation coefficient test, regression models (mediator model) and SPSS and AMOS statistical software have been used. Results: According to the findings of this research, body shame has a positive and significant relationship with symptoms of body deformity disorder (P<0.001). Body shame has a significant relationship with symptoms of body deformity disorder through the mediation of cognitive emotion regulation strategies (P<0.001). Conclusion: It can be concluded that cognitive emotion regulation strategies play a mediating role in the relationship between body shame and body deformity anxiety symptoms

A Prenatal Presentation of CDK13-Related Disorder with a Novel Pathogenic Variant

Cyclin-dependent kinase 13 (CDK13) is a member of the cyclin-dependent serine/threonine protein kinase family. Members of this family are well known for their essential roles as master switches in cell cycle control. CDK13-related disorder is a newly described genetic condition with characteristic clinical features including mild to severe intellectual disability, developmental delay, neonatal hypotonia, a variety of facial dysmorphism, behavioral problems, congenital heart defects, and structural brain abnormalities. We report a case of prenatal diagnosis of CDK13-related disorder. Detection of cystic hygroma with thickened nuchal fold led to prenatal genetic investigation, which identified a novel de novo likely pathogenic variant in the CDK13 gene (c.900C > G, p.Tyr300∗). Pregnancy was terminated and autopsy was performed. To our best knowledge, this is the first reported case of prenatal presentation of this condition with a detailed phenotypic description of the affected fetus

The mutation spectrum and ethnic distribution of Wilson disease, a review

Wilson's disease is a complicated medical condition caused by the accumulation of copper, mostly in the liver and brain. The genetic basis of Wilson's disease is attributed to the presence of pathogenic variants in the ATP7B copper-transporting gene, which prevents the excretion of copper through the biliary tract. To date, ATP7B remains the only identified gene that has been linked to the development of this disease. Our understanding of the disease has been associated with the identification of particular disease-causing variants that present specific impairments in copper transporters. It is crucial to identify the most frequent variant in terms of ethnicity to facilitate testing of its functionality. This study represents the initial comprehensive analysis of ATP7B variants, providing insights into the extensive range of disease-causing mutations. Here, we describe the 1275 distinct ATP7B variants documented so far, with particular emphasis on their regional and ethnic prevalence. The H1069Q missense variant is the most frequently reported in Europe, Northern America, and North Africa, whereas the R778L, C271*, and M645R variants are the most prevalent in the East Asian, Middle Eastern-South Asian, and South American populations, respectively. Acquiring such knowledge would facilitate the implementation of a selective mutation screening approach, targeting the most predominant variant identified within a specific ethnic group or geographic region for better diagnosis of the disease

New presentation of CLIFAHDD syndrome with a novel variant in NALCN gene: A report of a rare case

Key Clinical Message Congenital Contractures of Limbs and Face, Hypotonia, and Developmental Delay (CLIFAHDD) syndrome is a recently described type of distal arthrogryposis which unlike other subtypes is associated with developmental delay and various neurologic presentation. Epilepsy and ataxia have been reported. We add paroxysmal dyskinesia to the clinical spectrum. Understanding the molecular mechanism can help developing targeted therapy in future. Abstract This study resulted in identification of a novel variant in NALCN gene leading to autosomal dominant CLIFAHDD syndrome. Our patient presented with a form of nonepileptic paroxysmal dyskinesia. This is a new phenotype that has not been described previously

Association between IFN-γ +874A/T and IFN-γR1 (-611A/G, +189T/G, and +95C/T) Gene Polymorphisms and Chronic Periodontitis in a Sample of Iranian Population

Background. Interferon gamma (IFN-γ) is an immune regulatory cytokine that acts through its receptor and plays important role in progression of inflammatory disease such as chronic periodontitis (CP). The purpose of this study was to determine the differences in the distribution of IFN-γ (+874A/T) and IFN-γR1 (-611A/G, +189T/G, and +95C/T) gene polymorphisms among CP and healthy individuals and to investigate relationships between these polymorphisms and susceptibility to CP. Materials and Methods. 310 individuals were enrolled in the study including 210 CP patients and 100 healthy controls. Single nucleotide polymorphisms at IFN-γ (+874A/T) and IFN-γR1 (-611A/G, +189T/G, and +95C/T) were analyzed by ARMS-PCR and PCR-RFLP methods. Results. The significant difference was found in genotype and allele frequency of IFN-γ (+874A/T) gene polymorphism in chronic periodontitis patients and healthy controls. The distribution of genotypes and allele frequencies for IFN-γR1 (-611A/G, +189T/G, and +95C/T) were similar among the groups and no differences in the frequencies of alleles or genotypes of IFN-γR1 genetic polymorphisms variants between case and control groups were detected. Conclusion. The finding of this study showed that IFN-γ +874A/T gene polymorphism may affect susceptibility to CP, whereas IFN-γR1 genetic polymorphisms at -611A/G, +189T/G, and +95C/T were not associated with this disease

Chemoradiation in Nasopharyngeal Carcinoma: A 6-Year Experience in Tehran Cancer Institute

To determine the addition of value of neoadjuvant, concurrent and adjuvant chemotherapy to radiation in the treatment of nasopharyngeal carcinoma with regard to the overall survival (OS) and disease free survival (DFS) within a six year period in Tehran cancer institute. Files of all patients with nasopharyngeal carcinoma treated by radiotherapy with or without concurrent chemotherapy in a curative setting in Tehran cancer institute during the period of 1999-2005 were retrospectively reviewed.. A total of 103 patients with nasopharyngeal carcinoma had been treated during the study period with radiotherapy or chemoradiotherapy in our institute. There were 29 (28.2%) females and 74 (71.8%) males. The median age at the time of radiotherapy was 47 years old (range 9-75 years). The patients were followed 2 to 76 months with a median follow-up of 14 months. Time of first recurrence after treatment was 3-44 months with a median of 10 months.. Survival in 2 groups of patients treated with radiotherapy alone or chemoradiation did not have a significant difference (P>0.1). Two-year survival in patients treated with or without adjuvant chemotherapy and had local recurrence after treatment did not have significant difference (P>0.1). Two-year survival in patients with or without local recurrence after treatment did not have significant difference (P>0.1). A beneficial affect or a survival benefit of adjuvant/neoadjuvant chemotherapy and concurrent chemoradiation was not observed in Iranian patients

Association of macrophage migration inhibitory factor gene polymorphisms with chronic periodontitis in a South Eastern Iranian population

Background: Macrophage migration inhibitory factor (MIF) is a key proinflammatory mediator. It plays a vital role in immune response against the oral disease. MIF is a regulator of innate immunity, and bacterial antigens can stimulate serum level of this protein. In experimental gingivitis, the expression level of MIF increases and this increment positively correlates with oral plaque index. The single nucleotide polymorphisms in the gene encoding the MIF protein can control the function of MIF. The aim of the present study was a clarification of the associations between MIF-173 G/C, MIF 95 bp, and 189 bp insertion/deletion (I/D) polymorphisms and chronic periodontitis (CP) compared with healthy controls. Materials and Methods: This case–control study was carried out on 210 CP patients and 100 normal subjects. MIF-173 G/C and MIF 95 bp and 189 bp I/D polymorphisms were genotyped, using polymerase chain reaction–restriction fragment-length polymorphism (PCR-RFLP) and PCR, respectively. Allele and genotype frequencies of the variants were compared between patients and controls using Chi-square. test. The value of P < 0.05 was considered statistically significant. Results: The study findings showed that MIF-173 G/C polymorphism, especially the C allele increased the risk of CP. The 95-bp I/D polymorphism was not associated with CP and the 185-bp I/D variant was not polymorphic in our population. Conclusion: Therefore, MIF-137 G/C variant increased the risk of CP in the South East of the Iranian population. In other words, polymorphisms in MIF gene influence clinical outcome of CP infection and influence the susceptibility to disease. Further studies with larger sample sizes and different ethnicities are required to validate our findings