A Novel c.973G>T Mutation in the ε-subunit of the Acetylcholine Receptor Causing Congenital Myasthenic Syndrome in an Iranian Family.

Congenital myasthenic syndrome (CMS) constitutes a group of inherited disorders of neuromuscular junctions. The majority of postsynaptic syndromes result from mutations in the CHRNE gene that causes muscle nicotine acetylcholine deficiency. In this study, we report on a 2 and a half-year-old boy with normal developmental milestones and bilateral ptosis. Clinical courses, electrophysiological studies and molecular genetic analysis were assessed. Polymerase chain reaction (PCR) and direct DNA sequencing of the CHRNE gene were performed for the proband and all the family members. A novel homozygous missense mutation of c.973G>T was found in the CHRNE gene. Segregation studies were suggested to be the genetic cause of the disease. Using three in silico tools and the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) variant classification guidelines indicated that the novel variant c.973G>T was likely pathogenic. Our results recommended first screening of the CHRNE gene for pathogenic mutations in Iranian origin.

The rs2910164 variant is associated with reduced miR-146a expression but not cytokine levels in patients with type 2 diabetes.

PURPOSE: Previous reports have demonstrated that genetic variations in microRNAs regulome could affect microRNAs-mediated regulation. Therefore, in the present study we were aimed at (1) comparison of microRNA 146-a (miR-146a) peripheral blood mononuclear cells (PBMCs) and plasma levels between diabetic patients and controls, and (2) investigating the possible association of rs2910164 with miR-146a and its related target genes expression and also serum cytokine levels. METHODS: The study population consisted of 60 subjects including 30 type 2 diabetes (T2D) patients and 30 controls with determined genotypes for rs2910164. The RNA expression levels were determined by real-time PCR. Moreover, TNF-α, IL-6, IL-10 and IL-1ß serum levels were measured using ELISA method. RESULTS: Our results showed that the miR-146a expression levels were significantly decreased in PBMCs (P = 0.004) and plasma (P = 0.008) samples of patients with T2D compared to healthy participants. In addition, we observed that IRAK1 mRNA expression-but not TLR4, TRAF6 and NFĸB-was significantly increased in patients with T2D compared to controls (P = 0.028). The relative expression levels of miR-146a in plasma and PBMCs samples of diabetic patients with the rs2910164 GG genotypes were significantly higher than that in CC (P < 0.05). Moreover, no significant differences were found in miR-146a targets and cytokine levels between the rs2910164 different genotypes. CONCLUSION: Our study demonstrated that miR-146a circulating levels were significantly elevated in controls compared with T2D patients. In addition, we identified that rs2910164-C allele is associated with reduced expression levels of the miR-146a but not its mRNAs targets and cytokine levels in diabetic patients.

A novel mutation and variable phenotypic expression in a large consanguineous pedigree with Jalili syndrome.

PurposeJalili syndrome is an autosomal recessive disorder characterized by simultaneous appearance of cone-rod dystrophy (CRD) and amelogenesis imperfecta (AI). Mutations in CNNM4 gene have been identified as the underlying cause of the syndrome. In this study, we investigated a large affected family to identify the causative mutation.Patients and MethodsA seven-generation family with 24 members affected with Jalili syndrome were enrolled in the study. Comprehensive ophthalmologic and dental examinations were performed on them. The entire coding region of CNNM4 gene was sequenced for detection of potential mutations.ResultsOcular examinations showed nystagmus and photophobia along with early onset visual impairment. Fundoscopic exams revealed a spectrum of macular dystrophies in different family members, from macular coloboma and advanced form of beaten bronze macular dystrophy (bull's eye) to milder form of macular thinning along with a range of pigmentary changes and vascular attenuation in the posterior pole and periphery. Scotopic and photopic electro-retinographic responses (ERGs) were extinguished or significantly depressed. Mutation analysis revealed a novel mutation (c.1091delG) in homozygous form in the patients and as a heterozygous form in the normal carrier subjects.ConclusionWe identified a novel homozygous deleterious mutation in CNNM4 gene which causes Jalili syndrome.

The pre-mir-27a variant rs895819 may contribute to type 2 diabetes mellitus susceptibility in an Iranian cohort.

PURPOSE: The study was aimed at investigating the association between hsa-mir-27a polymorphism rs895819 (T/C) and type 2 diabetes mellitus (T2DM) susceptibility in a large Iranian cohort. METHODS: In this case-control study, the investigated population consisted of T2DM patients (n = 204) and sex- and age-matched controls (n = 209). We used the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) for genotyping. RESULTS: We observed significant differences between T2DM patients and controls for weight (p = 0.002), BMI (p < 0.001), systolic blood pressure (p < 0.001), diastolic blood pressure (p < 0.001), fasting plasma glucose (p < 0.001), triglyceride (p = 0.004) and LDL cholesterol (p = 0.051). Moreover, we found that genotype distributions were significantly different between groups (p < 0.05) and that the rs895819-C allele is more frequent in controls (p = 0.030, OR = 0.72, 95 % CI 0.53-0.97). CONCLUSION: Our study shows that rs895819 in hsa-mir-27a is associated with T2DM susceptibility and that the C allele conveyed a protective role against T2DM. Larger multicentric and specific functional studies will be necessary to obtain a deeper comprehension of the role of rs895819 and hsa-mir-27a and how they are involved in the development of diabetes.

Hepatitis B virus infection in patients with blood disorders: a concise review in pediatric study.

Childhood Hepatitis B virus (HBV) infection causes both medical and public health challenges. Infants who acquire HBV parentally have up to 90% risk of developing chronic HBV infection. It is now estimated that approximately 10% of worldwide cancers are attributable to viral infection, with the vast majority (>85 %) occurring in the developing world. In this distribution, elevated rate and prevalence of HBV marker have been found in patients with malignancies as compared to the general population. By reviewing the web-based search for all Persian and English types of scientific peer review published articles initiated using Iran Medex, MEDLINE/PubMed, CINAHL and other pertinent references on websites about HBV and HCV blood disorders. The high prevalence of HBV and HCV infective markers was detected in patients with different malignancies. Moreover, identification of high prevalence of HBV infective markers in leukemia patients proposed strong association between hepatitis viral infections and leukemia.

Highly selective and sensitive spectrophotometric determination of trace amounts of silver ion in surfactant media using 2-mercaptobenzoxazole.

A simple and accurate spectrophotometric method for determination of trace amounts of silver ion in tap and wastewater solution and photographic solutions has been described. The spectrophotometric determination of silver ion using 2-mercaptobenzoxazole (MBO) in the presence of Triton X-100 as nonionic surfactant has been carried out. The Beer's law is obeyed over the concentration range of 0.1-9.0 microg mL(-1) of Ag+ ion with the detection limits of 1.6 ng mL(-1). The influence of type and amount of surfactant, pH, complexation time and amount of ligand on sensitivity of method were optimized. Finally the repeatability, accuracy and the effect of interfering ions on the determination of silver ion were evaluated. There is a good agreement between results of proposed method and atomic absorption spectrometry.