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Objective: The objective of this article is to investigate the distinct features, morbidity and mortality of systemic lupus erythematosus (SLE) patients registered in rheumatology tertiary centers of Shiraz University of Medical Sciences from 2008 to 2018. Method: A cross-sectional study was conducted on registered patients by reviewing their medical records. The clinical presentations were classified based on each organ's distinct involvement. Result: Data of 1322 patients with a mean age of 40 at the time of the study were reviewed. The most common primary manifestation of the disease was arthralgia (37.5%), and the most common clinical presentation in course of the disease was skin involvement (61.8%). The most common cause of hospital admission was disease flare (27.8% (108/388)), and mortality was mainly due to pulmonary complications (27.5% (8/29)). Patients who had hypothyroidism had statistically significantly lower rates of constitutional symptoms (p = 0.006), gastrointestinal involvement (p = 0.024), hypertension (p = 0.002), headache (p = 0.019), depression (p = 0.049) and anemia (p = 0.014). Patients who presented with malar rash and photosensitivity in their course of disease were detected to have statistically significantly lower ages of disease onset (p = 0.013 and 0.003, respectively). Conclusion: This study is an update to an epidemiologic study conducted in 2008 in the south of Iran. By comparing results between the two studies, we have tried to investigate the change in morbidity and mortality of SLE during these years. [ABSTRACT FROM AUTHOR]

Background: Hypomyelinating leukodystrophy-9 (HLD-9) is caused by biallelic pathogenic variants in RARS1, which codes for the cytoplasmic tRNA synthetase for arginine (ArgRS). This study aims to evaluate the clinical, neuroradiological, and genetic characteristics of patients with RARS1-related disease and determine probable genotype-phenotype relationships., Methods: We identified three patients with RARS1 homozygous pathogenic variants. Furthermore, we performed a comprehensive review of the literature., Results: Homozygous variants of RARS1 (c.2T>C (p.Met1Thr)) were identified in three patients with HLD-9. Clinical symptoms were severe in all patients. Following the literature review, thirty HLD-9 cases from eight studies were found. The 33 patients' main symptoms were hypomyelination, language delay, and intellectual disability or developmental delay. The mean age of onset for HLD9 in the group of 33 patients with a known age of onset was 5.8 months (SD = 8.1). The interquartile range of age of onset was 0-10 months. Of the 25 variants identified, c.5A>G (p.Asp2Gly) was identified in 11 patients., Conclusion: Pathogenic variants in RARS1 decrease ArgRS activity and cause a wide range of symptoms, from severe, early onset epileptic encephalopathy with brain atrophy to a mild condition with relatively maintained myelination. These symptoms include the classic hypomyelination presentation with nystagmus and spasticity. Furthermore, the pathogenicity of the variation c.2T>C (p.Met1Thr) has been shown., (© 2024 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

White-Sutton Syndrome is one of the rare neurodevelopmental disorder inherited in an autosomal dominant manner, mainly caused by de novo mutations in the POGZ gene and shows many phenotypic signs such as intellectual disability, Autism Spectrum Disorder and other spectra. About 70 patients with this syndrome have been reported worldwide. In this paper, we have described different phenotypic features of the White-Sutton Syndrome with a brief review of recent literatures. Finally, we have reported an Iranian male with intellectual disability and visual impairment. We have explained the clinical symptoms of the patient and have compared the patient's phenotype with existing data from individuals with White-Sutton Syndrome. The results of Whole Exome Sequencing test, performed for the patient, declared the presence of a de novo mutation in POGZ gene and confirmed the White-Sutton Syndrome diagnosis., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Galloway-Mowat syndrome is a rare autosomal-recessive genetic disorder that is characterized by variety of complications such as neurological abnormalities and early-onset progressive kidney disease. Studies have been shown that pathogenic mutations in genes that belong to the KEOPS complex lead to Galloway-Mowat syndrome. Several pathogenic mutations in OSGEP gene, a member of the KEOPS complex, have been detected in Galloway-Mowat syndrome. Here we describe a 12-year-old male with intellectual disability, poor speech, seizures, microcephaly, and nephrotic syndrome that were in favor of Galloway-Mowat syndrome, born to a healthy Iranian consanguineous parents. Extracted genomic DNA from blood sample was used to perform whole-exome sequencing in the patient. The mutational screening revealed a novel homozygote OSGEP gene missense variant. Our finding established whole-exome sequencing as a valuable technic for the detection of rare variants., (© 2023. The Author(s) under exclusive licence to The Japan Society of Nephrology.)

Pathogenic variants in FAT1 gene have recently been described in association with coloboma, nephropathy, and facial dismorphism. Here we describe a 5-year-old Iranian boy with iris coloboma and nephropathy, born to an Iranian family. Extracted genomic DNA from blood sample was used to perform whole exome sequencing in the patient. The mutational screening revealed a homozygote Fat1 gene mutation c.5320A > G (p.17747Val), not previously reported in homozygote state in Iran. Our findings establish FAT1 as a gene with pleiotropic effects in human, emphasizing it as one of the causative genes in syndromic nephropathies., (© 2022. The Author(s) under exclusive licence to The Japan Society of Nephrology.)

Introduction: /objectives. Single nucleotide polymorphisms (SNPs) located at the 3'-UTR region of the target genes of microRNAs (miRNAs) can dysregulate their expression via disrupting the binding site of miRNAs. Interleukin-16 (IL-16) is involved in the pathogenesis of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In the current study, we assessed the possible association between rs1131445 polymorphism in IL-16 gene with risk and clinical characteristics of RA and SLE in the Iranian population., Methods: In this case-control study, 120 patients with RA, 120 patients with SLE, and 120 unrelated healthy subjects were collected to estimate rs1131445 (T > C) polymorphism in IL-16 gene using real-time PCR high-resolution melting (HRM) method., Results: Our results demonstrated considerable associations between TC genotype and C allele of rs1131445 with enhanced risk of RA (OR for TC genotype  = 3.01; 95%CI [1.667-5.526], P < 0.001; OR for C allele  = 1.96; 95%CI [1.314-2.941], P < 0.001). Besides, there was a marginal association between CC genotype and increased risk of RA (P: 0.031). However, there was an insignificant correlation between genotypes and allele frequencies of rs1131445 with incidence risk of SLE (P > 0.05). Moreover, stratification analysis indicated that the C allele in rs1131445 was linked with disease activity-associated laboratory parameters such as CRP and ESR in both RA and SLE patients, as well as the higher incidence of neurological symptoms in SLE subjects (P < 0.05)., Conclusion: These results proposed a significant association between IL-16 polymorphism and augmented risk of RA and clinical characteristics of RA and SLE., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background: Signal transducer and activator of transcription 3 (STAT3) is a major regulator of immune response and chronic inflammatory conditions acting through regulation of B cells, T-helper 17 (Th17) cells, and IL-17 production. Previous studies have demonstrated that dysregulation of STAT3 is crucial for SLE pathogenesis and disease severity. It is believed that single nucleotide polymorphisms (SNPs) located at the 3'-UTR sequence of the target genes could dysregulate their expression by disrupting the binding site of miRNAs. In the present study, we assessed the possible association between rs1053005 and rs1053023 SNPs at miRNA binding sites in the STAT3 gene and the risk of SLE in the Iranian population for the first time., Methods: 112 SLE cases and 120 healthy controls were genotyped for rs1053005 (A>G) and rs1053023 (A>G) polymorphisms in STAT3 using real-time PCR high resolution melting method (HRM)., Results: Our results revealed substantial associations between GG genotype and G allele of rs1053023 with enhanced risk of SLE (OR for GG genotype= 3.13; 95%CI [1.61-6.1], OR for G allele = 2.22; 95%CI [1.51-3.25]). However, no important correlations have been found between rs1053005 polymorphism and SLE susceptibility in this population ( p >0.05). Moreover, stratification analysis showed that these polymorphisms are correlated with parameters indicating disease activity and more severe course of the disease. These factors include some laboratory test results and clinical manifestations such as renal involvements., Conclusion: The current study suggests a significant association between STAT3 polymorphisms and augmented risk of SLE, clinical symptoms, disease activity, and severity.

Introduction/objectives: Systemic lupus erythematosus (SLE) is a multifactorial systemic autoimmune disease, in which genetic susceptibility plays a pivotal role. The nucleotide oligomerization domain 2 (NOD2) gene is one of the main regulators of chronic inflammatory conditions and could be involved in SLE pathogenesis. Single nucleotide polymorphisms (SNPs) in miRNA binding sites which are located in 3'UTR of the NOD2 gene could be associated with SLE risk by dysregulation of NOD2 expression. In the present study, we assessed the possible association between SNPs rs3135500 and rs3135499 in the NOD2 gene with SLE risk in the Iranian population., Methods: A case-control study using 110 SLE patients and 120 control subjects was undertaken to estimate rs3135500 (G > A) and rs3135499 (A > C) genotypes via real-time PCR high-resolution melting method (HRM)., Results: No significant association was observed between allele and genotype frequencies of rs3135500 and rs3135499 polymorphisms and SLE risk in this population (P > 0.05). However, there was an obvious association between rs3135500 (A allele) with laboratory factors that are associated with disease activity (P < 0.05) and some clinical manifestations that are associated with disease severity such as neurological symptoms, skin manifestations, renal involvements, and higher serum concentration of creatinine (P < 0.05). Besides, rs3135499 (C allele) was correlated with renal involvement and also the concentration of creatinine (P < 0.05). Moreover, in the patients group, the risk alleles in these polymorphisms were associated with lower age of onset (P < 0.05)., Conclusions: Our results suggest a substantial association between NOD2 polymorphisms with clinicopathological characteristics and SLE disease activity. Key Points • Single nucleotide polymorphisms (SNPs) in miRNA binding sites which are located in 3'UTR of the NOD2 gene could be associated with SLE risk by dysregulation of NOD2 expression. • Our results suggested that two miRSNPs (rs3135500 and rs3135499) in the NOD2 gene were meaningfully correlated with clinicopathological characteristics and disease activity of SLE., (© 2021. International League of Associations for Rheumatology (ILAR).)

Background: Rheumatoid arthritis (RA) is a complex systemic autoimmune disorder with multifactorial nature. Numerous previous studies have shown that several genes are involved in the pathogenesis and increased risk of RA. The Nod-like receptor pyrin domain containing 3 (NLRP3) is involved in the regulation of innate immunity and its upregulation has previously been reported in RA., Objective: To evaluate the correlation between 3 functional polymorphisms of NLRP3 and its gene expression and RA risk., Method: One hundred and fourteen patients with RA and 120 healthy participants were recruited to this case-control study. Genotyping of rs4612666 (intronic variant), rs10754558 (3UTR variant), and rs6672995 (downstream variant) were performed applying the real‑time polymerase chain reaction high‑resolution melting (HRM) method., Results: Based on logistic regression analysis, subjects with CC genotype and C allele in rs4612666 had increased risk of RA (OR for CC genotype= 3.10; 95%CI [1.78-8.26]/ OR for C allele= 2.00; 95%CI [1.45-3.10]). Furthermore, in the patient groups, there was a significant relationship between the concentration of C-reactive protein (CRP) and rs4612666 and rs10754558 polymorphism (p < 0.05). Besides, our results revealed no significant association between the genotype and allele frequency of rs10754558 and rs6672995 and the risk of RA (P> 0.05)., Conclusion: Our findings propose a significant association between rs4612666 polymorphism and increased risk of RA in the Iranian population. Moreover, rs4612666 and rs10754558 were correlated with disease activity.

Objective: Nod-like receptor pyrin domain containing 3 ( NLRP3 ) gene encodes an intracellular receptor whose dysregulation in systemic lupus erythematosus (SLE) has been reported in multiple studies. Activation of NLRP3 inflammasome leads to the induction of inflammatory response via cleaving and producing of specific cytokines. In the present study, we assessed the possible association between three functional polymorphisms in this gene and SLE risk in the Iranian population. These variants include two gain of function (rs4612666 and rs10754558) and one loss of function (rs6672995) which are correlated with modulation of expression of NLRP3 ., Methods: A case-control study involving 110 SLE patients and 116 control subjects was undertaken to estimate the frequency of rs4612666, rs10754558, and rs6672995 genotypes using real-time PCR high resolution melting method (HRM)., Results: Our findings revealed significant associations between GG genotype and G allele of rs10754558 with increased risk of SLE (OR for GG genotype = 2.82; 95%CI [1.45-5.46]/OR for G allele = 1.97; 95%CI [1.36-2.87]). Although, no significant associations were recognized between allele and genotype frequencies of rs4612666 and rs6672995 polymorphisms with SLE risk ( P  > 0.05). Also, our analysis revealed that the C allele in rs4612666 and G allele in rs10754558 was correlated with the severity of disease activity (P < 0.001). Moreover, these common variants were associated with lower age of onset and some clinical symptoms in the patient group, such as skin manifestation, neurological symptom and, renal involvement (P < 0.05)., Conclusion: This study demonstrates a substantial association between NLRP3 polymorphisms with increased risk, clinical symptoms, and the severity of disease activity of SLE.

MicroRNA-124 (miR-124) is known as an important regulator of the immune system and inflammatory response. Studies have reported that this miRNA is dysregulated in autoimmune disorders such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). A functional analysis demonstrated that rs531564 (C>G) affects the biogenesis of primary microRNA transcript-124 (pri-miR-124) and changes the expression of mature miR-124. In the present study, for the first time, we intended to evaluate the possible association between rs531564 polymorphism with SLE and RA risk.  In this case-control study, 110 patients with SLE, 115 patients with RA, and 120 healthy subjects were enrolled to evaluate rs531564 genotypes with real-time polymerase chain reaction (PCR) high resolution melting method. Our findings demonstrated that frequency of GC genotype and G allele were considerably higher in the control group than RA patients, demonstrating that that GC genotype and G allele have a protective effect for healthy individuals (GC vs CC; OR: 0.29; 95%CI [0.12,0.67] and G vs C; OR: 0.42; 95%CI [0.23,0.78]). However, no significant correlation was confirmed between allele and genotype frequencies of rs531564 with SLE risk (p>0.05). However, the G allele in rs531564 polymorphism was associated with serum level of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), anti-dsDNA antibody, C3, C4, and creatinine, and frequency of renal involvements in SLE patients (p<0.05). Moreover, in RA patients, the G was correlated with lower concentration ESR and CRP (p<0.001).  Our findings propose a considerable association between rs531564 polymorphism in the pri-miR-124 gene with susceptibility and clinical characteristics of RA and SLE in the Iranian population.

The nucleotide-binding oligomerization domain 2 (NOD2) is the key regulator of inflammatory responses and has been involved in the pathogenesis of rheumatoid arthritis (RA). Laboratory and in silico evaluations have demonstrated that some polymorphisms in 3'UTR of NOD2 gene could influence the secondary structure of this region and similarly thermodynamic features of hybridization site and finally deregulate the expression of NOD2. In the current study, for the first time, we evaluated the possible association between single nucleotide polymorphisms (SNPs) rs3135500 and rs3135499 in the NOD2 gene with RA risk in the Iranian population. One hundred and fifteen patients with RA and 120 healthy subjects were recruited in this case-control study. Genotyping of rs3135500 and rs3135499 polymorphisms were accomplished using the real‑time polymerase chain reaction high resolution melting (HRM) method. We found a substantial association of AA and AG genotypes in rs3135500 with the risk of RA (AA vs GG; OR=5.547; 95%CI [2.564-11.999]; p<0.001 and AG vs GG; OR=2.179; 95%CI [1.145-4.147]; p=0.017). Moreover, in the patient group, there was a significant relationship between the increased concentration of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) with rs3135500 (A allele) (p<0.05). However, there were no important associations between rs3135499 with the risk of RA (p>0.05). However, we found a noteworthy association of the C allele in rs3135499 with an increased level of CRP in patients (p>0.05). Our findings propose a considerable association between NOD2 polymorphisms with increased risk of RA and disease activity.

Introduction and Objectives: Long-term follow up of patients with hyper IgE syndrome (HIES), as a primary immunodeficiency disorder, has been poorly investigated. This study describes common clinical and immunological features of patients with HIES in the last 10 years in Shiraz University of Medical Sciences, Shiraz, Iran., Methods and Patients: In this cross-sectional study, the symptoms and medical records of 18 patients, who were diagnosed with HIES, were observed. Genetic and immunologic study was also performed., Results: Eighteen patients with the mean age of 13 years old were investigated. Ten patients were detected to have mutations in DOCK8 gene and autosomal recessive HIES (AR-HIES); and four patients were found with STAT3 mutation and autosomal dominant HIES (AD-HIES). So, 14 patients with known genetic results were considered for further data analysis. Food allergy, eczema, viral and skin infections were the major complications of AR-HIES patients. The major clinical complications of AD-HIES patients were pneumonia, skin infections and eczema. Food allergy and viral infection were significantly higher in DOCK8 deficient patients. The most common causes of hospitalization in both AR-HIES and AD-HIES patients were pneumonia, skin infections and sepsis. The most common cause of death was found to be sepsis., Conclusions: AD-HIES and AR-HIES cannot be differentiated only based on the clinical presentations. Genetic features are also necessary for better diagnosis. This study, summarizing the clinical, immunological and genetic information of the patients with AD-HIES and AR-HIES, may open a way for better diagnosis and management of HIES., (Copyright © 2018 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.)

This study investigates the possibility of acid mine drainage (AMD) generation in active and derelict mine waste piles in Sarcheshmeh Copper Mine produced in several decades, using static tests including acid-base accounting (ABA) and net acid-generating pH (NAGpH). In this study, 51 composite samples were taken from 11 waste heaps, and static ABA and NAGpH tests were carried out on samples. While some piles are acid producing at present and AMD is discharging from the piles, most of them do not show any indication on their AMD potential, and they were investigated to define their acid-producing potential. The analysis of data indicates that eight waste piles are potentially acid generating with net neutralization potentials (NNPs) of -56.18 to -199.3, net acid generating of 2.19-3.31, and NPRs from 0.18 to 0.44. Other waste piles exhibited either a very low sulfur, high carbonate content or excess carbonate over sulfur; hence, they are not capable of acid production or they can be considered as weak acid producers. Consistency between results of ABA and NAGpH tests using a variety of classification criteria validates these tests as powerful means for preliminary evaluation of AMD/ARD possibilities in any mining district. It is also concluded that some of the piles with very negative NNPs are capable to produce AMD naturally, and they can be used in heap leaching process for economic recovery of trace amounts of metals without applying any biostimulation methods.

Background: Anthropometry is the biologic science of human body measurement. Craniofacial anthropometry discusses the characteristics on the measures of different soft and hard tissues of the head and face, and it is considered an important paraclinical record for the growth and development of the index and also for the diagnosis and curing orthodontic matters. Studying the craniofacial anthropometrics ratios is very useful in sciences such as dentistry, medicine, maxillofacial surgery, growth and development studies, plastic surgery, bioengineering, and nonmedical branches such as respiratory equipment and eye-glasses industries., Objectives: The aims of this study were to determine Iranian cranial and facial anthropometric ratios and compare anthropometric ratios between Iranian and Canadian populations., Methods: This cross-sectional analytical study was done randomly on 564 four-to-eleven-year-old boys from Shirvan (North Khorasan, Iran) with normal face patterns. Facial and cranial ratios were estimated and compared. Data were analyzed by SPSS software. The mean values of these parameters were calculated .Finally, the regression line and the growth coefficient were determined for each parameter. Furthermore, the mean anthropometric measurement of Iranians was compared with Canadians. Student t test was used for comparing the measured values., Results: Iranian population when born has hypereuryprosopic face and hypercephalic cranium form. While getting older, the midface height increases, face becomes more prominent, chin becomes shorter, and the face and cranium change to eurycephalic and hyperleptoprosopic form, respectively. Comparison of results related to the face and cranium size between Iranian and Canadian boys (4-11 years old) showed that many craniofacial ratios have significant differences (P < 0.05)., Conclusions: Approximately, all of the anthropometric measurements in Iranian population and Canadians were significantly different. Considering the significant difference in the facial and cranial anthropologic ratios and size among Iranians and Canadians, the results obtained from Canadians should not be applied as criteria for treatment plans. Because of the wide population affinity combinations in Iran, more studies, with wider variations, should be conducted among different Iranian population affinity.