No Hot Spot Mutations CHRNE c.1327 delG, CHAT c.914T>C, and RAPSN c.264C>A in Iranian Patients with Congenital Myasthenic Syndrome

 AbstractObjectivesWe aimed to perform genetic testing and clinical data of patients with Congenital Myasthenic Syndrome, a rare disorder caused by mutations in genes encoding molecules expressed in the neuromuscular junction and constitutes fatigable muscle weakness. MethodsSixteen patients were screened in Taban Clinic, Tehran, Iran from 2014 to 2015 for the hot spot mutations in known CMSs genes (CHRNE, CHAT, RAPSN) based on clinical data. PCR was performed and then direct DNA sequencing was done for mutation identification.ResultsMost patients represented the criteria of Congenital Myasthenic Syndrome in view of early ptosis, motor delay, normal mental development, easy fatigability, decrement in repetitive nerve stimulation test of EMG-NCV and a negative result for antibody against of acetylcholine receptor. No variations were found in the mutational analysis of the CHRNE gene. Analysis of CHAT gene revealed c.358G>A (P. A120T) variation in 9 patients. In the gene RAPSN, polymorphism c.456T>C )P.Y152Y) and polymorphism c.193-15C>T (IVS1-15C>T) were identified in 11 and one patients, respectively.ConclusionThe common founder mutations of involved genes in CMSs could be very rare among ethnic Iranian. Screening of the entire genes would be efficient to distinguish the specific mutations in specific ethnicity

A case report of congenital myasthenic syndrome caused by a mutation in the CHRNE gene in the Iranian population

Congenital myasthenic syndrome (CMS) refers to a heterogeneous group of inherited disorders, characterized by defective transmission at the neuromuscular junction (NMJ). Patients with CMS showed similar muscle weakness, while other clinical manifestations are mostly dependent on genetic factors. This disease, caused by different DNA mutations, is genetically inherited. It is also associated with mutations of genes at NMJ, involving the acetylcholine receptor (AChR) subunits. Here, we present the case of a five-year-old Iranian boy with CMS, undergoing targeted sequencing of a panel of genes, associated with arthrogryposis and CMS. The patient had six affected relatives in his genetic pedigree chart. The investigations indicated a homozygous single base pair deletion at exon 12 of the CHRNE gene (chr17:4802186delC). This region was conserved across mammalian evolution and was not submitted to the 1000 Genomes Project database. Overall, the CHRNE variant may be classified as a significant variant in the etiology of CMS. It can be suggested that the Iranian CMS population carry regional pathogenic mutations, which can be detected via targeted and whole genome sequencing

Evaluation of the knowledge regarding vitamin D, and sunscreen use of female adolescents in Iran

Background Vitamin D (Vit D) deficiency/insufficiency is an important risk factor for several chronic conditions. We aimed to evaluate the knowledge and behavior of female adolescents with respect to the association between sunlight exposure, sunscreen use, and Vit D status. Methods This cross-sectional survey was performed in northeastern Iran, among 940 female adolescents in January 2015. Each subject completed a questionnaire containing items about demographic characteristics, knowledge about Vit D and their use of sunscreen. Serum Vit D levels were measured using an electrochemiluminescence method and dietary intake of Vit D was assessed using a Food Frequency Questionnaire. Statistical analyses were conducted using SPSS software. A P value < 0.05 was considered statistically significant. Results Few of the participants were aware of the biological functions of Vit D (8.8%), the causes of Vit D deficiency (16.7%), and the sources of Vit D (9.3%). Less than half of the participants used sunscreen during the day. The serum levels of Vit D in subjects who used sunscreen were significantly lower than those who did not (p = 0.004). However, there was no significant association between their knowledge about Vit D and serum Vit D, or dietary intake of Vit D. Conclusion There appears to be a lack of coherence between lifestyle, behavior and knowledge that may affect the Vit D status of adolescent girls in northeastern Iran. This information provides a basis for developing public health planning (workshops or training at the college level) for the prevention of Vit D deficiency especially in adolescent girls

Novel Homozygous Pathogenic Mutations of LAMA 2 Gene in patients with congenital muscular dystrophy

The laminin-α2 subunit is a protein that is encoded by the Laminin α 2 gene (LAMA2) which has the role of adhesion (attachment of cells to one another). Genetics consideration showed that mutation in LAMA2 caused a collection of muscle-wasting conditions called Muscular Dystrophy (MD). This disorder causes disconnection of the muscular cells and degeneration of the musculoskeletal system. In this study, we define the molecular consideration of 3 patients with laminin α 2 deficiency by clinical presentations of congenital muscular dystrophy (CMD). In this regard, 65 exons of LAMA2 gene were amplified by Polymerase Chain Reaction (PCR). Also, MLPA and NGS was done for all patients. Because of negativity of NGS, the gene sequence was performed. The results of searching for rearrangements of the LAMA2 gene enabled us to recognize homozygous pathogenic mutations c.2049_c.2050del, c.7156-2A&gt;G and c,1303C&gt;T. These mutations produce an out-of-frame transcript that will be degraded by nonsense-mediated decay. Therefore, we think these changes are pathogenic ones

Evaluating the association between ccr5delta32 polymorphism (Rs333) and the risk of breast cancer in a cohort of Iranian population

Funding Information: This manuscript was supported by the Student Research Committee of Mashhad University of science (Grant Numbers: 951734 & 961689).Peer reviewedPublisher PD

High-density lipoprotein lipid peroxidation as a molecular signature of the risk for developing cardiovascular disease: Results from MASHAD cohort.

High-density lipoprotein (HDL) function rather than level may better predict cardiovascular disease (CVD). However, the contribution of the impaired antioxidant function of HDL that is associated with increased HDL lipid peroxidation (HDLox) to the development of clinical CVD remains unclear. We have investigated the association between serum HDLox with incident CVD outcomes in Mashhad cohort. Three-hundred and&nbsp;thirty individuals who had a median follow-up period of 7 years were recruited as part of the cohort. The primary end point was cardiovascular event, including myocardial infarction, stable angina, unstable angina, or coronary revascularization. In both univariate/multivariate analyses adjusted for traditional CVD risk factors, HDLox was an independent risk factor for CVD (odds ratio, 1.62; 95% confidence interval, 1.41-1.86; p &lt; 0.001). For every increase in HDLox by 0.1 unit, there was an increase in CVD risk by 1.62-fold. In an adjusted analysis, there was a &gt;2.5-fold increase in cardiovascular risk in individuals with HDLox higher than cutoff point of 1.06 compared to those with lower scores, suggesting HDLox &gt; 1.06 is related to the impaired HDL oxidant function and in turn exposed to elevated risk of CVD outcomes (hazard ratio, 2.72; 95% CI, 1.88-3.94). Higher&nbsp;HDLox is a surrogate measure of reduced HDL antioxidant function that positively associated with cardiovascular events in a population-based cohort