An Iranian familial amyotrophic lateral sclerosis pedigree with p.Val48Phe causing mutation in SOD1: a genetic and clinical report

Objective(s): Amyotrophic lateral sclerosis (ALS), a fatal progressive neurodegenerative disorder, is the most common motor neuron disease in European populations. Approximately 10% of ALS cases are familial (FALS) and the other patients are considered as sporadic ALS (SALS). Among many ALS causing genes that have been identified, mutations in SOD1 and C9orf72 are the most common genetic causes of the disease. In Iranian patients, it has been shown that SOD1, as compared to C9orf72, plays a much more prominent role.  To date, more than 170 mutations have been reported in SOD1. Genotype/phenotype correlation with respect to either different causative genes or different mutations of a specific gene has not been well established.  Materials and Methods: Five exons of SOD1 and flanking intronic sequences of an Iranian FALS proband were screened for mutations by direct sequencing. Also, the clinical features of the proband were described. Results: Heterozygous p.Val48Phe causing mutation was identified in SOD1. Age at onset was 29 years and site of the first presentation was the lower extremity in the proband. Conclusion: The p.Val48Phe causing mutation appears to cause early onset of ALS

Molecular dynamics simulations of p-tert-butylcalix[4]arene with small guest molecules

Classical molecular dynamics simulations were used to study p-tert-butylcalix[4]arene inclusion compounds with xenon, nitrogen, hydrogen, methane, and sulfur dioxide guest molecules. The calixarene units were taken to be rigid and the intermolecular molecular interactions were modeled as a sum of the van der Waals interactions with parameters from the AMBER force field and electrostatic interactions. Simulations of the high-density \u3b1 phase and low-density \u3b20 phase of p-tert-butylcalix[4]arene were used to test the force field. The predicted densities of the two phases were found to agree with experimental measurements at 173 K to within 5\u2009%. Simulations were performed with guests placed inside the calixarene cages of the \u3b20 phase. Guest\u2013host ratios of 1:1 to 1:4 were considered. Changes in the unit-cell volume and density of the phases with the addition of guest molecules and the inclusion energies for the guests were determined. Finally, the dynamics of the guest motion inside the cages were characterized by determining the root-mean-square displacements and velocity autocorrelation functions of the xenon and nitrogen guests.NRC publication: Ye

A novel nonsense mutation in WNK1/HSN2 associated with sensory neuropathy and limb destruction in four siblings of a large Iranian pedigree

Abstract Background Hereditary sensory and autonomic neuropathy type 2 (HSAN2) is an autosomal recessive disorder with predominant sensory dysfunction and severe complications such as limb destruction. There are different subtypes of HSAN2, including HSAN2A, which is caused by mutations in WNK1/HSN2 gene. Methods An Iranian family with four siblings and autosomal recessive inheritance pattern whom initially diagnosed with HSAN2 underwent whole exome sequencing (WES) followed by segregation analysis. Results According to the filtering criteria of the WES data, a novel candidate variation, c.3718C > A in WNK1/HSN2 gene that causes p.Tyr1025* was identified. This variation results in a truncated protein with 1025 amino acids instead of the wild-type product with 2645 amino acids. Sanger sequencing revealed that the mutation segregates with disease status in the pedigree. Conclusions The identified novel nonsense mutation in WNK1/HSN2 in an Iranian HSAN2 pedigree presents allelic heterogeneity of this gene in different populations. The result of current study expands the spectrum of mutations of the HSN2 gene as the genetic background of HSAN2A as well as further supports the hypothesis that HSN2 is a causative gene for HSAN2A. However, it seems that more research is required to determine the exact effects of this product in the nervous system

The association between OSA and glycemic control in diabetes

Background: Obstructive sleep apnea (OSA) is the most common sleep-realted respiratory disorder. It is frequently comorbid with cardiovascular, cerebrovascular, and metabolic diseases and is commonly observed in populations with these comorbidities. Investigators aimed to assess the effect of OSA on glycemic control in patients with diabetes. Methods: In this cross-sectional study, 266 adult patients with diabetes mellitus (DM) attending the outpatient endocrinology clinic at the Guilan University of Medical Sciences were enrolled. Patients completed a checklist that included demographic characteristics, factors, and laboratory results in addition to Berlin and STOP-BANG questionnaires to evaluate the risk of OSA. Data were analyzed by independent t-test, Mann–Whitney U test, and Chi-squared or Fisher's exact tests using the Statistical Package for the Social Sciences (SPSS) version 17. Results: A total of 266 patients with DM were enrolled in this study (34.6% males, mean age 47.00 ± 19.04 years). Based on the Berlin Questionnaire, 38.6% of all participants were at high risk of developing OSA. Based on the STOP-BANG Questionnaire (SBQ), 45.1% were at moderate and high risks. Additionally, this questionnaire showed a significant difference between low and moderate-to-severe groups regarding sex, age, body mass index (BMI), neck size, other chronic diseases, types of DM, use of insulin, Berlin Questionnaire, fasting blood sugar (FBS), and mean HbA1c. Conclusions: Based on the SBQ, our results indicated a significant relationship between OSA and glycemic control according to mean HbA1c and FBS. Therefore, by controlling the OSA, we may find a way to acheieve better glycemic control in diabetic patients

Potential role of FKBP5 single‐nucleotide polymorphisms in functional seizures

Abstract Objective We investigated the associations between FKBP5 single‐nucleotide polymorphisms (SNPs) and functional seizures (FS). Methods Seventy patients with FS, 140 with major depressive disorder (MDD), and 140 healthy controls were studied. Their DNAs were analyzed for the rs1360780 in the 3′ region and rs9470080 in the 5′ region of the FKBP5. Childhood trauma questionnaire and hospital anxiety and depression scale were used. Results Patients with FS and those with MDD had less GG and more AA genotypes in both rs9470080 and rs1360780 SNPs compared with those in healthy controls. Similar results were observed for allelic frequencies. There were no significant differences between FS and MDD groups in terms of genotype and allelic frequencies for both SNPs. The results of multinomial logistic regression analysis showed that FKBP5 polymorphisms were not associated with the diagnosis. Significance Patients with FS and those with MDD had significantly different genotypes in both rs9470080 and rs1360780 SNPs compared with those in healthy controls. However, it seems that FKBP5 polymorphisms were not associated with FS in the absence of depression. Further genetic investigations of patients with FS may increase our understanding of the neurobiological underpinnings of this condition, but such studies should be large enough and very well designed; they should include a comparison group with depression in addition to a healthy control group