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Objective We studied the clinical and molecular features of a family with hypertrophic cardiomyopathy (HCM). Background A very heterogeneous disease affecting the heart muscle, HCM is mostly caused by variants in the proteins of sarcomeres. The detection of HCM pathogenic variants can affect the handling of patients and their families. Methods Whole-exome sequencing (WES) was performed to assess the genetic cause(s) of HCM in a consanguineous Iranian family. Results Missense likely pathogenic variant c.1279C>T (p.Arg427Cys) within exon 7 of the LMNA gene (NM_170707) was found. The segregations were confirmed by polymerase chain reaction–based Sanger sequencing. Conclusions Variant c.1279C>T (p.Arg427Cys) in the LMNA gene seemed to have been the cause of HCM in the family. A few LMNA gene variants related to HCM phenotypes have been recognized so far. Identifying HCM genetic basis confers significant opportunities to understand how the disease can develop and, by extension, how this progression can be arrested. Our study supports WES effectiveness for first-tier variant screening of HCM in a clinical setting. [ABSTRACT FROM AUTHOR]

Background: Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are inherited X-linked disorders resulting from alterations in the dystrophin gene. Genotype-phenotype matching studies have revealed a link between disease severity, the amount of muscle dystrophin, and the extent of mutation/deletion on the dystrophin gene. This study aimed to assess the relationship between genetic alterations in the dystrophin gene and the clinical status of patients with dystrophinopathies among the Iranian population. Methods: This cross-sectional study examined 54 patients with muscle weakness caused by abnormalities in the dystrophin gene at a hospital affiliated to Isfahan University of Medical Sciences, Isfahan, Iran, in 2021. The participants' demographic information, including age, family history of muscle dystrophies, and family history of other medical diseases as well as the type of muscular dystrophy were recorded. Furthermore, the number and region of deleted exons based on dystrophy types were also evaluated using multiplex ligation-dependent probe amplification (MLPA). The patients' gaits were also assessed as using a wheelchair, the presence of waddling gaits, or toe gaits. The patients' clinical status and the coexistence of pulmonary, bulbar, and mental conditions were also examined and compared between the two groups of dystrophinopathies. Results: In this study, 54 patients with dystrophinopathy with the mean age of 16.63 ± 12.10 years were evaluated, of whom 22 (40.7%) and 30 (55.6%) patients were classified as BMD and DMD, respectively. The most affected regions with deleted exons were exons 45-47 (n = 5) and 45-48 (n = 4) in patients with BMD, while exons 45, 48-52, 51-55, and 53 (2 cases per exon) were the most common affected exons in patients with DMD. Further analyses revealed that deletions in exons 45-47 and 51-55 were significantly associated with older and younger ages at the onset of becoming wheelchair-bound in patients with dystrophy, respectively. The hotspot range in both BMD and DMD was within exons 45-55 (n = 15 for each group); 63% of the patients had alterations on the dystrophin gene within this range [30 patients (68.18%) in the BMD group, 15 patients (53.57%) in the DMD group]. Conclusion: Exon deletion was the most common genetic alteration in patients with dystrophinopathies. No significant difference was observed between DMD and BMD regarding the number of deleted exons. Deletions in exons 45-47 and 51-55 were linked to later and earlier onset of becoming wheelchair-bound, respectively. [ABSTRACT FROM AUTHOR]

Background & Objective: Leptin is an adipocyte-derived hormone with a critical role in energy balance. As demonstrated by previous investigations, leptin acts as a proliferative and angiogenic factor in cancer cells. However, results regarding its role in colorectal cancer are still inconclusive. We aimed to evaluate serum leptin and tissue expression of leptin receptor (Ob-R) in normal and malignant samples of colorectal. Methods: Serum and tissue samples from pathology-confirmed colorectal cancer patients and normal controls referring to a university hospital of Mazandaran were obtained during 2019-21. ELISA and immunohistochemistry were applied to determine leptin and Ob-R expression respectively. Results: A total of 90 samples belonging to 46 normal and 44 CRC patients were enrolled. Normal and CRC groups included 32 (69.56%) and 21 (47.72%) female subjects respectively. The average leptin concentration in the normal group was 115.80 and, in the patient, group was 124.47 ng/mL (P=0.897). CRC cases showed an insignificantly higher Ob-R detection rate (P=0.086). Conclusion: There was no significant difference in leptin and Ob-R expression between CRC patients and normal subjects. Thus, leptin and its receptor may not be useful as a biomarker of CRC. [ABSTRACT FROM AUTHOR]

Background: Ion channel dysfunction in the brain can lead to impairment of neuronal membranes and generate several neurological diseases, especially neurodevelopmental disorders. Methods: In this study, we set out to delineate the genotype and phenotype spectrums of 14 Iranian patients from 7 families with intellectual disability (ID) and/or developmental delay (DD) in whom genetic mutations were identified by next-generation sequencing (NGS) in 7 channel-encoding genes: KCNJ10, KCNQ3, KCNK6, CACNA1C, CACNA1G, SCN8A, and GRIN2B. Moreover, the data of 340 previously fully reported ID and/or DD cases with a mutation in any of these seven genes were combined with our patients to clarify the genotype and phenotype spectrum in this group. Results: In total, the most common phenotypes in 354 cases with ID/DD in whom mutation in any of these 7 channel-encoding genes was identified were as follows: ID (77.4%), seizure (69.8%), DD (59.8%), behavioral abnormality (29.9%), hypotonia (21.7%), speech disorder (21.5%), gait disturbance (20.9%), and ataxia (20.3%). Electroencephalography abnormality (33.9%) was the major brain imaging abnormality. Conclusion: The results of this study broaden the molecular spectrum of channel pathogenic variants associated with different clinical presentations in individuals with ID and/or DD. [ABSTRACT FROM AUTHOR]

Background: Retinoblastoma (RB) is a common neoplastic disease in children, leading to high mortality if not diagnosed and treated timely. Mutations in both versions of the Retinoblastoma1 (RB1) gene are responsible for this disease. A wide range of mutations has been reported throughout the RB1 gene. Objectives: The present study aimed to assess the concordance of paternal and maternal RB-1 gene mutation with clinical manifestation and disease staging in patients suffering from RB. Methods: This cross-sectional study was performed on 23 patients with unilateral or bilateral RB. Paternal and maternal peripheral blood samples were extracted for genome analysis. Information related to clinical manifestations and disease staging was collected from the patients' hospital records. Multiplex-ligation dependent probe amplification (MLPA) method or Sanger sequencing method was employed to assess the gene mutation and its genomic pattern. Results: No significant association was revealed between the presence of both maternal and paternal RB1 gene mutations and the disease staging, while the study could show a significant relationship between the presence and heterozygous pattern of RB1 gene mutation and the presence of disease-related clinical manifestations that bilateral involvement was strongly associated with the presence of a heterozygous pattern of gene mutation compared to unilateral involvement (P = 0.001). Conclusions: This study showed a significant correlation between the presence of RB1 gene mutation and bilateral involvement in RB, but the association between the disease staging and gene mutation remains insignificant. [ABSTRACT FROM AUTHOR]

This cross-sectional study investigated the associations between urinary sodium (UNa) to potassium (UK) ratio, different phenotypes of elevated blood pressure (BP), and microalbuminuria (MAU) in a cohort of the Tehran Lipid and Glucose Study (TLGS). Adult participants (n = 1782, mean age of 43.0 ± 13.7 years and 46.0% were men) were recruited (2015-2017) for measurements of spot urinary metabolites, i.e., Na, K, creatinine (Cr), microalbumin, and BP. Multinomial logistic regression was used to estimate the relative risk ratios (RRR) of elevated BP phenotypes [i.e., isolated systolic (ISH), diastolic (IDH), and systolic-diastolic (SDH) hypertension], and binary logistic regression was used to estimate odds ratios (ORs) of MAU across quintile categories and per each SD-increment of UNa-K ratio. Mean UNa, UK, and its ratio was 137 ± 57.4, 72.1 ± 36.6 mmol/L, and 2.31 ± 1.41, respectively. Subjects with UNa-K > 3.14 had higher prevalence of ISH (3.4 vs. 1.1%), SDH (11.0 vs. 6.2%), and MAU (14.1 vs. 6.2%) (P for all < 0.05). Highest compared to the lowest UNa-K ratio values (> 3.14 vs. <1.23) was associated with an increased probability of SDH (RRR = 1.79, 95% CI 1.09-3.19) and MAU (OR = 2.53, 95% CI 1.23-5.20). Every 1 SD-increment of the UNa-K ratio was associated with a 29 and 38% increased chance of having SDH and MAU, respectively. Our findings imply that a high UNa-K ratio may be a potential risk factor for elevated BP and renal dysfunction., Competing Interests: Declarations Ethics approval and consent to participate Written informed consent was obtained from all participants. The ethics research committee of the Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran, approved the study protocol. The study protocol was carried out according to the relevant guidelines expressed in the Declaration of Helsinki. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Alteration in the etiology of pediatric bloodstream infections (BSIs) and antimicrobial resistance (AMR) is not well known during the Coronavirus disease 2019 (COVID-19) pandemic. This study aimed to investigate the impact of the COVID-19 pandemic on pediatric BSIs and alteration in antimicrobial resistance phenotypes in Gram-positive bacteria., Methods: The frequency of BSIs among children under 18 years old was retrospectively recorded in a tertiary children's hospital in Tehran, Iran from February 2020 to December 2022. The status of COVID-19 infection using reverse transcription polymerase chain reaction, bacteremia/fungemia according to BACTEC 9120 Culture System results, characterization of bacteria using biochemical tests, and antimicrobial susceptibility patterns for Gram-positive bacterial isolates using disk diffusion method were determined. Statistical analysis was done to measure the correlation of COVID-19 infection with BSIs and AMR., Results: Out of 13,345 COVID-19 tests and 4,194 BACTEC blood culture requests, bacteremia/fungemia were confirmed in 10.37% (435/4,194) of the patients who requested both tests simultaneously. The COVID-19 infection was confirmed in 25.3% (110/435) of the patients with bacteremia/fungemia. The infection with characterized Gram-positive bacteria (GPB) and fungi was detected in 32.3% (140/433) and 8.31% (36/433) of the cases, respectively. Coagulase-negative Staphylococcus (CNS, 72, 16.62%), S. aureus (36, 8.3%), and Enterococcus spp. (22, 5%) were among the common isolates. Candida spp. and non-Candida yeasts were detected in 6.7% and 13.4% of the cases, respectively. A positive correlation was shown between the CNS bacteremia and COVID-19 infection (p-value = 0.019). Antibiotic susceptibility testing results showed the highest frequency of resistance to azithromycin among CNS, azithromycin and tetracycline among S. aureus and tetracycline among Enterococcus spp. Methicillin-resistance phenotype in the S. aureus (MRSA) and coagulase-negative Staphylococcus spp. (MR-CNS) was detected in 40% and 61.5% of the strains, respectively and the Enterococci were resistant to vancomycin in 33.3% of the isolates., Conclusion: A decline in the trend of BSIs by GPB and an increase in AMR was shown in children during the COVID-19 pandemic. Increasing antibiotic resistance is a concern; however, chloramphenicol, linezolid, and vancomycin remain active against common causes of GPB-BSIs., (© 2024. The Author(s).)

Aim: We investigated the association of a 3-year change in body weight (BW) and regression to normal glucose regulation (NGR) among different phenotypes of pre-diabetes (Pre-DM), i.e., isolated impaired glucose tolerance (iIGT), isolated impaired fasting glucose (iIFG) and combined IFG-IGT., Research Design and Methods: 1458 Pre-DM subjects (iIFG = 618, iIGT = 462, and IFG-IGT = 378) were assessed for 3-year change-percent in BW (2006-2008 to 2009-2011) and then followed up to 2015-2017, within the national cohort of Tehran Lipid and Glucose Study (TLGS). Binary logistic regression models were used to estimate the probability (odds ratio, ORs) of regression to NGR across categories of 3-year BW change (i.e., ≥5% BW loss, <5% BW loss, BW gain) in different phenotypes of Pre-DM., Results: The mean age of the participants was 53.0 ± 13.7, and 46.8% were men. Over a median of 6 years of follow-up, the rate of regression to normoglycemia was 50.6, 43.2, and 12.7% in iIGT, iIFG, and combined IFG-IGT, respectively. The baseline-adjusted mean of 3-year BW change was not significantly different across Pre-DM phenotypes (0.68 ± 0.19, 0.32 ± 0.22, and 0.23 ± 0.24 kg, in iIFG, iIGT, and IFG-IGT). Three-year BW loss ≥5% was associated with a greater NGR probability in iIGT than other phenotypes (OR = 4.29 vs. 3.90 and 2.84 in IFG-IGT and iIFG, respectively). A modest reduction (<5% of initial BW) resulted in an increased chance of Pre-DM regression among subjects with iIGT (OR = 1.61, 95% CI = 1.03-2.52) but not iIFG or IFG-IGT phenotypes., Conclusion: Short-term intensive BW loss (≥5% of initial BW) increased NGR probability in all Pre-DM phenotypes, with an order of iIGT > combined IFG-IGT > iIFG. Only iIGT takes advantage of moderate BW loss (<5% of initial BW) to increase the chance of Pre-DM regression., Competing Interests: Declaration of competing interest All authors declare that they have no competing interests., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Aims: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic cardiac disorder characterized by unexplained left ventricular hypertrophy. It can cause a wide spectrum of clinical manifestations, ranging from asymptomatic to heart failure and sudden cardiac death (SCD). Approximately half of HCM cases are caused by variants in sarcomeric proteins, including α-tropomyosin (TPM1). In this study, we aimed to characterize the clinical and molecular phenotype of HCM in an Iranian pedigree with SCD., Methods and Results: The proband and available family members underwent comprehensive clinical evaluations, including echocardiography, cardiac magnetic resonance (CMR) imaging and electrocardiography (ECG). Whole-exome sequencing (WES) was performed in all available family members to identify the causal variant, which was validated, and segregation analysis was conducted via Sanger sequencing. WES identified a novel missense variant, c.761A>G:p.D254G (NM&#95;001018005.2), in the TPM1 gene, in the proband, his father and one of his sisters. Bioinformatic analysis predicted it to be likely pathogenic. Clinical features in affected individuals were consistent with HCM., Conclusions: The identification of a novel TPM1 variant in a family with HCM and SCD underscores the critical role of genetic screening in at-risk families. Early detection of pathogenic variants can facilitate timely intervention and management, potentially reducing the risk of SCD in individuals with HCM., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Nosocomial infections are a global problem in hospitals all around the world. It is considered a major health problem, especially in developing countries. The increase in the patient's stay in hospitals has increased the mortality rate, and consequently, the costs drastically increase. The main purpose of using disinfectants in the hospital environment is to reduce the risk of nosocomial infections. Ethylene diamine tetra acetic acid (EDTA) causes lysis and increases susceptibility to antimicrobial agents in the planktonic form of bacteria. This substance affects the permeability of the outer membrane of bacteria. It also prevents the formation of biofilms by bacteria., Materials and Methods: In the current study, 120 isolates of Acinetobacter baumannii (A. baumannii) were confirmed by phenotypic and genotypic methods. Antibiogram was performed and then the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of isolates against 5% sodium hypochlorite, ethanol %70, sayasept-HP 2%, chlorhexidine 2%, dettol 4/8% were evaluated. In addition, the disinfectant effect was re-evaluated with the mixture of EDTA solution. All isolates were examined for biofilm presence by crystal violet staining method in triplicates and repeated three times for each strain. Also for all isolates detection of efflux pump genes (Qac-E, qacE-Δ1, SUG-E) by PCR technique was done., Results: Antibiogram results of A. baumannii showed that 6.7% were Multi-drug-resistant (MDR), and 89.2% were Extensively drug-resistant (XDR) isolates. The highest effect of disinfectants was related to 5% sodium hypochlorite, and the least effect was 70% ethanol. EDTA increases the efficacy of selected disinfectants significantly. The highest prevalence of the efflux pump genes was related to SUG-E (95%) and Qac-E (91.7%), and, the qacE-Δ1 gene with 12.5%. The biofilm production rate was 91.3% among all isolates., Conclusion: The best and safest way to disinfect hospital floors and surfaces is to choose the right disinfectants, and learn how to use them properly. In this study, a mixture of disinfectants and EDTA had a significant effect on bactericidal activity. it was found that improper use of disinfectants, especially the use of sub-inhibitory dilutions, increases the resistance of bacteria to disinfectants., (© 2024. The Author(s).)

Background: Arrhythmogenic cardiomyopathy (ACM) characterized by progressive myocardial loss and replacement with fibro-fatty tissue is a major cause of sudden cardiac death (SCD). In particular, ACM with predominantly left ventricular involvement, known as arrhythmogenic left ventricular cardiomyopathy (ALVC), has a poor prognosis., Methods: The proband underwent whole-exome sequencing (WES) to determine the etiology of ALVC. Family members were then analyzed using PCR and Sanger sequencing. Clinical evaluations including 12-lead ECG, transthoracic echocardiography, and cardiac MRI were performed for all available first-degree relatives., Results: WES identified two variants in the FLNC (c.G3694A) and JUP (c.G1372A) genes, the combination of which results in ALVC and SCD., Conclusion: The present study comprehensively investigates the involvement of two discovered variants of FLNC and JUP in the pathogenesis of ALVC. More study is necessary to elucidate the genetic factors involved in the etiology of ALVC., (© 2024. The Author(s).)

Background: There is a high prevalence of inherited bleeding disorders in Iran, such as hemophilia A (HA) and hemophilia B (HB). This study aimed to analyze the molecular and clinical profiles of patients with HB., Methods: A single-center study was conducted among patients with severe HB between March 20, 2000, and June 31, 2023. The polymerase chain reaction (PCR) amplification was used for all of the major regions, such as the promoter, the exons, the adjacent intronic regions, and the untranslated regions of the F9 gene. Finally, Sanger sequencing was performed on the PCR products., Results: A total of 111 HB patients (17 with HB [Leyden +] and 94 with HB [Leyden -]) were enrolled in this study. Among 94 patients with HB (Leyden -), 59 (62.8 %) had missense, 21 (22.3 %) had nonsense, and 8 (8.5 %) had frameshift mutations. Moreover, the most frequent pathogenic variant in HB (Leyden +) was c.-17 A>G in this study., Conclusion: The results of this study confirm that HB is caused by a wide range of molecular defects in Iran. Thus, by knowing the genotypes and phenotypes, we would be able to stratify the patients which is important in terms of their management and outcome., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The ultra-rare autosomal recessive genetic disorder, You-Hoover-Fong Syndrome (YHFS), is caused by defects in the TELO2 gene and is characterized by intellectual disability, developmental delay, and ocular impairments. This study aims to contribute to a better understanding of YHFS by reviewing previous cases and introducing a novel variant in a new case., Methods: Whole exome sequencing (WES) was conducted on the proband to identify genetic variants, and Sanger sequencing was used to confirm variants within the family. This article presents a comprehensive collection of reported cases of YHFS, incorporating both molecular and clinical data, through an extensive literature search and analysis of English-language studies published until June 2023., Results: Using WES, a novel homozygous missense variant, c.1799A > G (p. Tyr600Cys), was identified in the TELO2 gene in a 4-year-old Iranian male patient. Novel clinical features, including choanal atresia and clubfoot, were also identified. A comprehensive literature review identified 27 patients with YHFS, with 20 variants in the TELO2 gene. Missense pathogenic variants were the most common type of pathogenic variant, and the most common features were microcephaly and intellectual impairment., Conclusion: This study presents the first case of pathogenic variants in TELO2 gene in Iran, expands the genotypic and phenotypic spectrum of YHFS and contributes to the growing body of literature pertaining to YHFS. Furthermore, our findings highlight the importance of genetic testing for non-consanguineous carrier screening, as compound heterozygosity may be a significant factor in the development of YHFS. Further research is needed to clarify the molecular mechanisms underlying YHFS pathogenesis., (© 2024. Fondazione Società Italiana di Neurologia.)

Background: Autosomal recessive non-syndromic hearing loss (NSHL) and cone dystrophies (CODs) are highly genetically and phenotypically heterogeneous disorders. In this study, we applied the whole exome sequencing (WES) to find the cause of HL and COD in an Iranian consanguineous family with three affected individuals., Methods: Three members from an Iranian consanguineous family who were suffering from NSHL and visual impairment were ascertained in this study. Comprehensive clinical evaluations and genetic analysis followed by bioinformatic and co-segregation studies were performed to diagnose the cause of these phenotypes. Data were collected from 2020 to 2022., Results: All cases showed congenital bilateral NSHL, decreased visual acuity, poor color discrimination, photophobia and macular atrophy. Moreover, cornea, iris and anterior vitreous were within normal limit in both eyes, decreased foveal sensitivity, central scotoma and generalized depression of visual field were seen in three cases. WES results showed two variants, a novel null variant (p.Trp548Ter) in the PDE6C gene causing COD type 4 (Achromatopsia) and a previously reported variant (p.Ile84Thr) in the PDZD7 gene causing NSHL. Both variants were found in the cis configuration on chromosome 10 with a genetic distance of about 8.3 cM, leading to their co-inheritance. However, two diseases could appear independently in subsequent generations due to crossover during meiosis., Conclusions: Here, we could successfully determine the etiology of a seemingly complex phenotype in two adjacent genes. We identified a novel variant in the PDE6C gene, related to achromatopsia. Interestingly, this variant could cooperatively cause visual disorders: cone dystrophy and cone-rod dystrophy., (© 2024. The Author(s).)

Background and Aim: There is limited evidence to support the relationship between dietary patterns and metabolic phenotypes. Therefore, this study aimed to assess the association of dietary patterns with metabolic phenotypes among a large sample of Iranian industrial employees. Methods: This cross-sectional study was conducted among 3,063 employees of Esfahan Steel Company, Iran. Using exploratory factor analysis, major dietary patterns were obtained from a validated short form of food frequency questionnaire. The metabolic phenotypes were defined according to Adult Treatment Panel III guidelines. The independent-sample t -test, one-way analysis of variance, χ 2 test, and multivariable logistic regression were applied to analyze data. Results: There were significant associations between dietary patterns and metabolic phenotypes, suggesting the necessity of nutritional interventions in industrial employees to improve metabolic phenotype, health outcomes, and, therefore, job productivity in the workforce population. Conclusion: There were significant associations between dietary patterns and metabolic phenotypes, suggesting the necessity of nutritional interventions in industrial employees to improve metabolic phenotype, health outcomes, and, therefore, job productivity in the workforce population.

Curtobacterium flaccumfaciens (Microbacteriaceae), a plant-pathogenic coryneform species includes five pathovars with valid names and a number of proposed - but unvalidated - new members. In this study, phenotypic features and DNA similarity indexes were investigated among all C. flaccumfaciens members. Results showed that the C. flaccumfaciens pv. poinsettiae strains causing bacterial canker of Euphorbia pulcherrima in the USA as well as the orange-/red-pigmented strains of C. flaccumfaciens pv. flaccumfaciens pathogenic on dry beans in Iran are too distinct from each other and from the type strain of the species to be considered members of C. flaccumfaciens. Hence, the latter two groups were elevated at the species level as C. poinsettiae sp. nov. (ATCC 9682 T  = CFBP 2403 T  = ICMP 2566 T  = LMG 3715 T  = NCPPB 854 T as type strain), and C. aurantiacum sp. nov. (50R T  = CFBP 8819 T  = ICMP 22071 T as type strain). Within the emended species C. flaccumfaciens comb. nov., yellow-pigmented strains causing bacterial wilt of dry beans and those causing bacterial canker of Euphorbia pulcherrima in Europe were retained as C. flaccumfaciens pv. flaccumfaciens and C. flaccumfaciens pv. poinsettiae, respectively; while taxonomic position of the sugar beet pathogen C. flaccumfaciens pv. beticola ATCC BAA144 PT was confirmed. The newly described onion pathogen C. allii was also reclassified as C. flaccumfaciens pv. allii with the pathotype strain LMG 32517 PT . Furthermore, C. flaccumfaciens pv. basellae causing bacterial leaf spot of malabar spinach (Basella rubra) was transferred to C. citreum pv. basellae with ATCC BAA143 PT as pathotype., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: Obesity is a worldwide health concern with serious clinical effects, including myocardial infarction (MI), stroke, cardiovascular diseases (CVDs), and all-cause mortality. The present study aimed to assess the association of obesity phenotypes and different CVDs and mortality in males and females by simultaneously considering the longitudinal and survival time data., Methods: In the Tehran Lipid and Glucose Study (TLGS), participants older than three years were selected by a multi-stage random cluster sampling method and followed for about 19 years. In the current study, individuals aged over 40 years without a medical history of CVD, stroke, MI, and coronary heart disease were included. Exclusions comprised those undergoing treatment for CVD and those with more than 30% missing information or incomplete data. Joint modeling of longitudinal binary outcome and survival time data was applied to assess the dependency and the association between the changes in obesity phenotypes and time to occurrence of CVD, MI, stroke, and CVD mortality. To account for any potential sex-related confounding effect on the association between the obesity phenotypes and CVD outcomes, sex-specific analysis was carried out. The analysis was performed using packages (JMbayes2) of R software (version 4.2.1)., Results: Overall, 6350 adults above 40 years were included. In the joint modeling of CVD outcome among males, literates and participants with a family history of diabetes were at lower risk of CVD compared to illiterates and those with no family history of diabetes in the Bayesian Cox model. Current smokers were at higher risk of CVD compared to non-smokers. In a logistic mixed effects model, odds of obesity phenotype was higher among participants with low physical activity, family history of diabetes and older age compared to males with high physical activity, no family history of diabetes and younger age. In females, based on the results of the Bayesian Cox model, participants with family history of diabetes, family history of CVD, abnormal obesity phenotype and past smokers had a higher risk of CVD compared to those with no history of diabetes, CVD and nonsmokers. In the obesity varying model, odds of obesity phenotype was higher among females with history of diabetes and older age compared to those with no history of diabetes and who were younger. There was no significant variable associated with MI among males in the Bayesian Cox model. Odds of obesity phenotype was higher in males with low physical activity compared to those with high physical activity in the obesity varying model, whereas current smokers were at lower odds of obesity phenotype than nonsmokers. In females, risk of MI was higher among those with family history of diabetes compared to those with no history of diabetes in the Bayesian Cox model. In the logistic mixed effects model, a direct and significant association was found between age and obesity phenotype. In males, participants with history of diabetes, abnormal obesity phenotype and older age were at higher risk of stroke in the Bayesian Cox model compared to males with no history of diabetes, normal obesity phenotype and younger persons. In the obesity varying model, odds of obesity phenotype was higher in males with low physical activity, family history of diabetes and older age compared to those with high physical activity, no family history of diabetes and who were younger. Smokers had a lower odds of obesity phenotype than nonsmokers. In females, past smokers and those with family history of diabetes were at higher risk of stroke compared to nonsmokers and females with no history of diabetes in the Bayesian Cox model. In the obesity varying model, females with family history of diabetes and older ages had a higher odds of obesity phenotype compared to those with no family history of diabetes and who were younger. Among males, risk of CVD mortality was lower in past smokers compared to nonsmokers in the survival model. A direct and significant association was found between age and CVD mortality. Odds of obesity phenotype was higher in males with a history of diabetes than in those with no family history of diabetes in the logistic mixed effects model., Conclusions: It seems that modifications to metabolic disorders may have an impact on the heightened incidence of CVDs. Based on this, males with obesity and any type of metabolic disorder had a higher risk of CVD, stroke and CVD mortality (excluding MI) compared to those with a normal body mass index (BMI) and no metabolic disorders. Females with obesity and any type of metabolic disorder were at higher risk of CVD(, MI and stroke compared to those with a normal BMI and no metabolic disorders suggesting that obesity and metabolic disorders are related. Due to its synergistic effect on high blood pressure, metabolic disorders raise the risk of CVD., (© 2024. The Author(s).)

Background: Neurofibromatosis type I (NF1) is a genetic disorder characterized by the tumor's development in nerve tissue. Complications of NF1 can include pigmented lesions, skin neurofibromas, and heart problems such as cardiomyopathy. In this study, we performed whole-exome sequencing (WES) on an Iranian patient with NF1 to identify the genetic cause of the disease., Methods: Following clinical assessment, WES was used to identify genetic variants in a family with a son suffering from NF1. No symptomatic manifestations were observed in other family members. In the studied family, in silico and segregation analysis were applied to survey candidate variants., Results: Clinical manifestations were consistent with arrhythmogenic cardiomyopathy (ACM). WES detected a likely pathogenic heterozygous missense variant, c.3277G > A:p.Val1093Met, in the NF1 gene, confirmed by PCR and Sanger sequencing. The patient's parents and brother had a normal sequence at this locus., Conclusions: Although there is no cure for NF1, genetic tests, such as WES, can detect at-risk asymptomatic family members. Furthermore, cardiac evaluation could also help these patients before heart disease development., (© 2024. The Author(s).)

Background: To investigate the genetics of early-onset progressive cerebellar ataxia in Iran, we conducted a study at the Children's Medical Center (CMC), the primary referral center for pediatric disorders in the country, over a three-year period from 2019 to 2022. In this report, we provide the initial findings from the national registry., Methods: We selected all early-onset patients with an autosomal recessive mode of inheritance to assess their phenotype, paraclinical tests, and genotypes. The clinical data encompassed clinical features, the Scale for the Assessment and Rating of Ataxia (SARA) scores, Magnetic Resonance Imaging (MRI) results, Electrodiagnostic exams (EDX), and biomarker features. Our genetic investigations included single-gene testing, Whole Exome Sequencing (WES), and Whole Genome Sequencing (WGS)., Results: Our study enrolled 162 patients from various geographic regions of our country. Among our subpopulations, we identified known and novel pathogenic variants in 42 genes in 97 families. The overall genetic diagnostic rate was 59.9%. Notably, we observed PLA2G6, ATM, SACS, and SCA variants in 19, 14, 12, and 10 families, respectively. Remarkably, more than 59% of the cases were attributed to pathogenic variants in these genes., Conclusions: Iran, being at the crossroad of the Middle East, exhibits a highly diverse genetic etiology for autosomal recessive hereditary ataxia. In light of this heterogeneity, the development of preventive strategies and targeted molecular therapeutics becomes crucial. A national guideline for the diagnosis and management of patients with these conditions could significantly aid in advancing healthcare approaches and improving patient outcomes., (© 2024. The Author(s).)

Background: Data on the epidemiology of inflammatory bowel disease (IBD) in the Middle East are scarce. We aimed to describe the clinical phenotype, disease course, and medication usage of IBD cases from Iran in the Middle East., Methods: We conducted a cross-sectional study of registered IBD patients in the Iranian Registry of Crohn's and Colitis (IRCC) from 2017 until 2022. We collected information on demographic characteristics, past medical history, family history, disease extent and location, extra-intestinal manifestations, IBD medications, and activity using the IBD-control-8 questionnaire and the Manitoba IBD index, admissions history, history of colon cancer, and IBD-related surgeries., Results: In total, 9746 patients with ulcerative colitis (UC) (n=7793), and Crohn's disease (CD) (n=1953) were reported. The UC to CD ratio was 3.99. The median age at diagnosis was 29.2 (IQR: 22.6,37.6) and 27.6 (IQR: 20.6,37.6) for patients with UC and CD, respectively. The male-to-female ratio was 1.28 in CD patients. A positive family history was observed in 17.9% of UC patients. The majority of UC patients had pancolitis (47%). Ileocolonic involvement was the most common type of involvement in CD patients (43.7%), and the prevalence of stricturing behavior was 4.6%. A prevalence of 0.3% was observed for colorectal cancer among patients with UC. Moreover,15.2% of UC patients and 38.4% of CD patients had been treated with anti-tumor necrosis factor (anti-TNF)., Conclusion: In this national registry-based study, there are significant differences in some clinical phenotypes such as the prevalence of extra-intestinal manifestations and treatment strategies such as biological use in different geographical locations., (© 2024 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

CHD3 heterozygous variants are associated with Snijders Blok-Campeau syndrome (SBCS) which consists of intellectual disability (ID), macrocephaly, and dysmorphic facies. Most reported variants are missense or loss of function clustered within the ATPase/helicase domain of the protein. We report a severe neurocognitive phenotype caused by biallelic CHD3 variants in two siblings, each inherited from a mildly affected parent. Male and female siblings were referred to the Genetics Clinic due to severe ID and profound dysmorphism. The parents are first cousins of Iranian descent with borderline intellectual abilities. Exome sequencing was performed for the affected female and her parents. A single homozygous candidate variant in the CHD3 gene was detected in the proband: c.5384&#95;5389dup. p.Arg1796&#95;Phe1797insTrpArg, resulting in an in-frame insertion of 2 amino acids located outside the ATPase/helicase domain at the C-terminal region of CHD3-encoding residues. This variant is classified as likely pathogenic according to ACMG guidelines. The variant was detected in a heterozygous state in each parent. Both affected siblings were homozygous, while their unaffected brother did not carry the variant. Biallelic CHD3 variants cause a severe neurodevelopmental syndrome that is distinguishable from SBCS. We assume that the variant type (in-frame insertion) and location may enable CHD3 biallelic variants., (© 2023 Wiley Periodicals LLC.)

Objective: Intellectual developmental disorder (IDD) type 5 is an autosomal dominant (AD) disorder and is characterized by intellectual disability (ID), psychomotor developmental delay, variable autism phenotypes, microcephaly, and seizure. IDD can be caused by mutations in the SYNGAP1 gene, which encodes a Ras GTPase-activating protein. This study revealed a novel de novo nonsense variant in SYNGAP1. The identification of such variants is essential for genetic counseling in patients and their families., Methods: Exome sequencing implicated the causative variant. Sanger sequencing and cosegregation analyses were used to confirm the variant. Multiple in silico analysis tools were applied to interpret the variant using the American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines., Results: The de novo NM&#95;006772.3(SYNGAP1):c.3685C>T variant was identified in an 11-year-old boy with severe intellectual disability, neurodevelopmental delay, speech disorder, ataxia, specific dysmorphic facial features, and aggressive behavior., Conclusion: The current study findings expand the existing knowledge of variants in SYNGAP1 that have been previously associated with nonsyndromic intellectual disability and autism, extending the spectrum of phenotypes associated with this gene. The data have implications for genetic diagnosis and counseling in similar phenotypic presentations., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This study investigates the risk of chronic kidney disease (CKD) across four metabolic phenotypes: Metabolically Healthy-No Obesity (MH-NO), Metabolically Unhealthy-No obesity (MU-NO), Metabolically Healthy-Obesity (MH-O), and Metabolically Unhealthy-Obesity (MU-O). Data from the Tehran Lipid and Glucose Study, collected from 1999 to 2020, were used to categorize participants based on a BMI ≥ 30 kg/m 2 and metabolic health status, defined by the presence of three or four of the following components: high blood pressure, elevated triglycerides, low high-density lipoprotein, and high fasting blood sugar. CKD, characterized by a glomerular filtration rate < 60 ml/min/1.72 m 2 . The hazard ratio (HR) of CKD risk was evaluated using Cox proportional hazard models. The study included 8731 participants, with an average age of 39.93 years, and identified 734 incidents of CKD. After adjusting for covariates, the MU-O group demonstrated the highest risk of CKD progression (HR 1.42-1.87), followed by the MU-NO group (HR 1.33-1.67), and the MH-O group (HR 1.18-1.54). Persistent MU-NO and MU-O posed the highest CKD risk compared to transitional states, highlighting the significance of exposure during early adulthood. These findings emphasize the independent contributions of excess weight and metabolic health, along with its components, to CKD risk. Therefore, preventive strategies should prioritize interventions during early-adulthood., (© 2024. The Author(s).)

Background: Being able to model a growth curve using three or four non-linear functional parameters could help explain the growth phenomenon in a precise way and would allow the comparison of an animal's development rate, optimize management and feeding strategies and guide animal production strategies., Objective: The goal of this study was to estimate the genetic parameters of growth traits of Isfahan indigenous chicken in Iran and to determine the best non-linear model describing the growth curve., Methods: The prediction of additive genetic parameters was performed using the REML method by WOMBAT. Direct heritability of the studied traits and genetic correlations between them were obtained. The Logistic, Gompertz, von Bertalanffy, Brody, Negative exponential, Weibull, Janoschek and Bridges models were compared based on the coefficient of determination (R 2 ), mean square error (MSE) and akaike information criterion., Results: The Gompertz model was identified as the best model for describing the growth curve for Isfahan native chicken. The heritability of maturity weights (A), initial weight (B) and maturity rate (K) parameters were 0.223 ± 0.002, 0.016 ± 0.005 and 0.087 ± 0.001, respectively., Conclusion: This study shows that Isfahan indigenous chicken has the genetic potential for improving growth and reproduction based on their desirable heritabilities and correlations using appropriate models., (© 2024 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Staphylococcus lugdunensis is a coagulase-negative Staphylococcus species that may cause various infections with unusual severity. In spite of the administration of various antibiotics, infections caused by such bacteria are become resistant significantly. Transmission of antibiotic resistance genes, especially by Integron structures, exacerbates the prevalence of resistant strains. To investigate the antibiotic susceptibility pattern of S. lugdunensis as a new emergence in burns, the presence of integron classes (I, II, III) was performed in recent study. Sampling for this study was carried out over a period of 13 months (January 2017 to February 2018) from Amir-Al-Momenin burn center of southwest of Iran, affiliated with Shiraz University of Medical Sciences. Twenty-eight isolates of S. lugdunensis were confirmed by phenotypic tests. The presence of integron classes was evaluated by PCR technique and specific primers. The majority of studied infectious agents were seen in ICU with 28.57%. The prevalence of class I and II integrons was 7 (25.00%) and 2 (7.14%), respectively, in S. lugdunensis isolates, whereas no integron III was found. No significant association was seen between antibiotic resistance and the present integrons (P > .05). Since the prevalence of S. lugdunensis strains as a new emergence infection is increasing in clinical settings especially burns, preventing drug resistance in these isolates is inevitable. So knowing the epidemiology pattern of new emerging infections and their resistant pattern is very helpful in infection control and save hospitalized patients life. [ABSTRACT FROM AUTHOR]

Objectives: The present study aimed to investigate the correlation of genotype-phenotype in patients with cystic fibrosis (CF) in the Azeri-Turkish population, Iran. Materials and Methods: In this descriptive-analytical study which was conducted according to Registry Center of Cystic Fibrosis, 206 patients with CF were investigated from 2001 to 2017. The data included clinical, laboratory, and genetic results. Descriptive statistics, chi-square test, and independent t test were applied using SPSS version 21.0. The odds ratio with 95% confidence interval and P < 0.05 were considered significant. Results: Thirty-one variants and 47 genotypes were observed. The ?F508 genotype (the most common genotype), especially homozygous and compound heterozygous genotypes were significantly different from other genotypes for chronic sinopulmonary disease, gastrointestinal and nutritional abnormalities, and salt loss syndromes, with a higher sweat test measures, higher mortality rate, and complications. Conclusions: Except for ?F508, the rest of mutations were the same, and milder clinical course, and most mutations belonged to this group. The challenge in cystic fibrosis consists of no detected mutations and high heterogeneity of cystic fibrosis transmembrane conductance regulator (CFTR) mutations. [ABSTRACT FROM AUTHOR]

• Detecting genetic defects in a large number of SCID patients. • Molecular diagnosis is a critical step for genetic counseling, carrier detection, and prenatal diagnosis in SCID patients. • Applying rational ways based on immunological and clinical findings can be very effective in managing the disease and reducing costs. Severe combined immunodeficiency (SCID) is the most severe form of primary immunodeficiency disorders that is characterized by impaired early T lymphocyte differentiation and is variably associated with abnormal development of other lymphocyte lineages. SCID can be caused by mutations in more than 20 different genes. Molecular diagnosis in SCID patients contributes to genetic counseling, prenatal diagnosis, treatment modalities, and overall prognosis. In this cohort, the clinical, laboratory and genetic data related to Iranian SCID patients were comprehensively evaluated and efficiency of stepwise sequencing methods approach based on immunophenotype grouping was investigated Clinical and laboratory data from 242 patients with SCID phenotype were evaluated. Molecular genetic analysis methods including Sanger sequencing, targeted gene panel and whole exome sequencing were performed on 62 patients. Mortality rate was 78.9% in the cohort with a median follow-up of four months. The majority of the patients had a phenotype of T-NK-B+ (34.3%) and the most severe clinical manifestation and highest mortality rate were observed in T-NK-B- SCID cases. Genetic mutations were confirmed in 50 patients (80.6%), of which defects in recombination-activating genes (RAG1 and RAG2) were found in 16 patients (32.0%). The lowest level of CD4+ and CD8+ cells were observed in patients with ADA deficiency (p = 0.026) and IL2RG deficiency (p = 0.019), respectively. Current findings suggest that candidate gene approach based on patient's immunophenotype might accelerate molecular diagnosis of SCID patients. Candidate gene selection should be done according to the frequency of disease-causing genes in different populations. Targeted gene panel, WES and WGS methods can be used for the cases which are not diagnosed using this method. [ABSTRACT FROM AUTHOR]

Background: Cannabis is a historically, culturally, and economically significant crop in human societies, owing to its versatile applications in both industry and medicine. Over many years, native cannabis populations have acclimated to the various environments found throughout Iran, resulting in rich genetic and phenotypic diversity. Examining phenotypic diversity within and between indigenous populations is crucial for effective plant breeding programs. This study aimed to classify indigenous cannabis populations in Iran to meet the needs of breeders and breeding programs in developing new cultivars., Results: Here, we assessed phenotypic diversity in 25 indigenous populations based on 12 phenological and 14 morphological traits in male and female plants. The extent of heritability for each parameter was estimated in both genders, and relationships between quantitative and time-based traits were explored. Principal component analysis (PCA) identified traits influencing population distinctions. Overall, populations were broadly classified into early, medium, and late flowering groups. The highest extent of heritability of phenological traits was found in Start Flower Formation Time in Individuals (SFFI) for females (0.91) Flowering Time 50% in Individuals (50% of bracts formed) (FT50I) for males (0.98). Populations IR7385 and IR2845 exhibited the highest commercial index (60%). Among male plants, the highest extent of Relative Growth Rate (RGR) was observed in the IR2845 population (0.122 g.g - 1 .day - 1 ). Finally, populations were clustered into seven groups according to the morphological traits in female and male plants., Conclusions: Overall, significant phenotypic diversity was observed among indigenous populations, emphasizing the potential for various applications. Early-flowering populations, with their high RGR and Harvest Index (HI), were found as promising options for inclusion in breeding programs. The findings provide valuable insights into harnessing the genetic diversity of indigenous cannabis for diverse purposes., (© 2024. The Author(s).)

Background: Pontocerebellar hypoplasia is an umbrella term describing a heterogeneous group of prenatal neurodegenerative disorders mostly affecting the pons and cerebellum, with 17 types associated with 25 genes. However, some types of PCH lack sufficient information, which highlights the importance of investigating and introducing more cases to further elucidate the clinical, radiological, and biochemical features of these disorders. The aim of this study is to provide an in-depth review of PCH and to identify disease genes and their inheritance patterns in 12 distinct Iranian families with clinically confirmed PCH., Methods: Cases included in this study were selected based on their phenotypic and genetic information available at the Center for Comprehensive Genetic Services. Whole-exome sequencing (WES) was used to discover the underlying genetic etiology of participants' problems, and Sanger sequencing was utilized to confirm any suspected alterations. We also conducted a comprehensive molecular literature review to outline the genetic features of the various subtypes of PCH., Results: This study classified and described the underlying etiology of PCH into three categories based on the genes involved. Twelve patients also were included, eleven of whom were from consanguineous parents. Ten different variations in 8 genes were found, all of which related to different types of PCH. Six novel variations were reported, including SEPSECS, TSEN2, TSEN54, AMPD2, TOE1, and CLP1. Almost all patients presented with developmental delay, hypotonia, seizure, and microcephaly being common features. Strabismus and elevation in lactate levels in MR spectroscopy were novel phenotypes for the first time in PCH types 7 and 9., Conclusions: This study merges previously documented phenotypes and genotypes with unique novel ones. Due to the diversity in PCH, we provided guidance for detecting and diagnosing these heterogeneous groups of disorders. Moreover, since certain critical conditions, such as spinal muscular atrophy, can be a differential diagnosis, providing cases with novel variations and clinical findings could further expand the genetic and clinical spectrum of these diseases and help in better diagnosis. Therefore, six novel genetic variants and novel clinical and paraclinical findings have been reported for the first time. Further studies are needed to elucidate the underlying mechanisms and potential therapeutic targets for PCH., (© 2024. The Author(s).)

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.)

Background: Say-Barber-Biesecker-Young-Simpson (SBBYS) (OMIM #603736, Ohdo syndrome variant) is a rare type of severe blepharophimosis intellectual disability syndrome, which is generally characterized by a global developmental delay, distinctive facial features, and intellectual disability with multiple congenital anomalies, including skeletal involvement, missing, or underdeveloped kneecaps, and genital anomalies, in affected males. It has been shown that mutations in the KAT6B gene, which is a lysine acetyltransferase-encoding gene, have been associated with SBBYS syndrome. All the known variants are dominant de novo mutations that result in protein truncation., Case Presentation: A 14-year-old Iranian Azeri boy with an intellectual disability, distinct dysmorphic facial features such as open-mouth expression, sparse medial eyebrows, widely spaced upward-slanted eyes, epicanthal folds, broad nasal bridge, low-set ears, anteverted ears, short philtrum, hypertelorism, microphthalmia is presented in this case study. Cryptorchidism was reported. Neurologically, the patient presented with poor eye contact, hypotonia, and speech difficulties. In the skeletal X-ray, underdeveloped kneecaps with some new features were observed., Conclusion: We present the first case of SBBYS syndrome in association with some new anomaly features in the Iranian population. Based on this diagnosis, we could provide the patient with a suitable plan of management as well as appropriate genetic counseling for his family., (© 2023. The Author(s).)

Background: There has been lack of evidence on the association between healthy dietary patterns and metabolic health status of adolescents. The present study aimed to evaluate the association between alternative healthy eating index (AHEI) and metabolic health status among a relatively representative sample of Iranian adolescents with overweight/obesity., Methods: Adolescents with extra body weight (n = 203, aged 12-18 y), were selected for this cross-sectional study by a multistage cluster random-sampling method. Habitual dietary intakes and diet quality of individuals were assessed using validated food frequency questionnaire and AHEI-2010, respectively. Data on other covariates were also gathered by pre-tested questionnaires. To determine fasting glucose, insulin and lipid profiles, fasting blood samples were collected. Participants were categorized as having metabolically healthy overweight/obesity (MHO) or metabolically unhealthy overweight/obesity (MUO) phenotypes, based on two approaches (International Diabetes Federation (IDF) and combination of IDF with Homeostasis Model Assessment Insulin Resistance (HOMA-IR))., Results: The overall prevalence of MUO was 38.9% (based on IDF criteria) and 33.0% (based on IDF/HOMA-IR criteria). After considering all potential confounders, participants in highest tertiles of AHEI-2010 had lower odds of MUO profile according to both IDF (OR = 0.05; 95% CI: 0.01-0.15) and IDF/HOMA-IR (OR = 0.05; 95% CI: 0.02-0.19) definitions. This association was stronger in adolescents with overweight compared with obese ones and also among girls than boys. Moreover, each unit increase in AHEI-2010 score was associated with lower risk of MUO based on both criteria., Conclusions: Higher adherence to AHEI-2010 was inversely associated with odds of MUO in Iranian adolescents with overweight/obesity., (© 2024. The Author(s).)

Lodging is one of the most important limiting environmental factors for achieving the maximum yield and quality of grains in cereals, including wheat. However, little is known about the genetic foundation underlying lodging resistance (LR) in wheat. In this study, 208 landraces and 90 cultivars were phenotyped in two cropping seasons (2018-2019 and 2019-2020) for 19 LR-related traits. A genome-wide association study (GWAS) and genomics prediction were carried out to dissect the genomic regions of LR. The number of significant marker pairs (MPs) was highest for genome B in both landraces (427,017) and cultivars (37,359). The strongest linkage disequilibrium (LD) between marker pairs was found on chromosome 4A (0.318). For stem lodging-related traits, 465, 497, and 478 marker-trait associations (MTAs) and 45 candidate genes were identified in year 1, year 2, and pooled. Gene ontology exhibited genomic region on Chr. 2B, 6B, and 7B control lodging. Most of these genes have key roles in defense response, calcium ion transmembrane transport, carbohydrate metabolic process, nitrogen compound metabolic process, and some genes harbor unknown functions that, all together may respond to lodging as a complex network. The module associated with starch and sucrose biosynthesis was highlighted. Regarding genomic prediction, the GBLUP model performed better than BRR and RRBLUP. This suggests that GBLUP would be a good tool for wheat genome selection. As a result of these findings, it has been possible to identify pivotal QTLs and genes that could be used to improve stem lodging resistance in Triticum aestivum L., (© 2024. The Author(s).)

Familial adenomatous polyposis (FAP) is an autosomal dominant colorectal cancer syndrome that is characterized by the development of multiple adenomas in the colon and rectum with high penetrance rates. This disease has specific features like the occurrence of pathogenic variations in the APC gene and diverse FAP phenotypes due to the occurrence region. In this study we aimed to evaluate pathogenic variants in exons of the APC gene in Iranian patients with FAP. A total of 35 FAP individuals were referred to the gastroenterology ward of Taleghani Hospital. As the aim of the study was to study the germline variations in the participants, the peripheral blood was collected and after the DNA extraction, PCR, and Sanger sequencing processes for the APC gene, the results were evaluated by the ACMG classification guidelines to report their pathogenicity. Accordingly, out of eight specific detected variants, three of them were novel, and the rest were reported previously. These eight variants were all truncating protein and pathogenic, and they were limited to 849-1378 codons. Overall, detected variants revealed discrepancies and parallels with previous reported cases in terms of quantity, occurrence region, and association with demographic and clinicopathological characteristics of patients. The spectrum of detected variants and the patient's phenotype showed distinct characteristics, such as occurrence in specific regions and the absence of extracolonic symptoms like Congenital hypertrophy of the retinal pigment epithelium (CHRPE). These findings open the path to comprehending the typical symptoms, their rarity, and their occurrence in the Iranian population and also due to the facts, we found that the studying of the APC gene alone for diagnosing FAP disease is not sufficient, and considering other genes are completely rational in the case of sequencing and studying the variants.

Background: Duchene Muscular Disorder (DMD) is a severe X-linked recessive neuromuscular disease. Previous reports predicted that one-third of cases with a fatal X-linked recessive disease will be caused by a novel mutation, and the mutation rate for DMD seems to be higher in males., Objective: A novel mutation in the DMD gene DMD (NM&#95;004006.3):c.92A>G (p.Lys31Arg) is suggested for males because of their heterozygous mothers carrying the mutant alleles., Method: Whole Exome Sequencing (WES) was done for a 25-year-old female followed by the screening of the novel mutation in her parents and her brother by the Sanger sequencing technique. Some in silico analyses were run to find the putative alterations in wild-type and mutant structures by PolyPhen-2 and Mupro. Notably, SWISS-MODEL was performed to build a reliable model for the mutant allele based on the PDB ID: 1DXX structure. Also, superimposition was done by PyMol., Results: WES analysis revealed three novel mutations including DLD (exon13:c.G1382A:p. G461E), ABCA3 (exon12:c.G1404C:p.W468C), and DMD (exon2:c.A92G:p.K31R) in the case. Focusing on DMD mutation, Sanger sequencing of the patient's parents and brother indicated no mutant allele in her mother and brother but a mutant allele in her father as a hemizygous pattern. In silico analyses showed no considerable change regarding pathogenic impact., Conclusion: In conclusion, our findings revealed no pathogenic effect of the new mutation (K31R) of the DMD gene in an Iranian 25-year-old woman. Because of the DMD importance in preclinical diagnosis, these data may shed a light on the diagnosis of this mutation in future pregnancies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Cystic fibrosis (CF) is an autosomal recessive disease caused by the inheritance of two mutant cystic fibrosis transmembrane conductance regulator (CFTR) alleles, one from each parent. Autosomal recessive disorders are rarely associated with germline mutations or mosaicism. Here, we propose a case of paternal germline mutation causing CF. The subject also had an identifiable maternal mutant allele. We identified the compound heterozygous variants in the proband through Sanger sequencing, and in silico studies predicted functional effects on the protein. Also, short tandem repeat markers revealed the de novo nature of the mutation. The maternal mutation in the CFTR gene was c.1000C > T. The de novo mutation was c.178G > A, p.Glu60Lys. This mutation is located in the lasso motif of the CFTR protein and, according to in silico structural analysis, disrupts the interaction of the lasso motif and R-domain, thus influencing protein function. This first reported case of de novo mutation in Asia has notable implications for molecular diagnostics, genetic counseling, and understanding the genetic etiology of recessive disorders in the Iranian population.

Background: Dilated cardiomyopathy (DCM) is a major cause of sudden cardiac death and heart failure. Up to 50% of all DCM cases have a genetic background, with variants in over 250 genes reported in association with DCM. Whole-exome sequencing (WES) is a powerful tool to identify variants underlying genetic cardiomyopathies. Via WES, we sought to identify DCM causes in a family with 2 affected patients., Methods: WES was performed on the affected members of an Iranian family to identify the genetic etiology of DCM. The candidate variant was segregated via polymerase chain reaction and Sanger sequencing. Computational modeling and protein-protein docking were performed to survey the impact of the variant on the structure and function of the protein., Results: A novel single-nucleotide substitution (G > A) in exon 9 of MED12, c.1249G > A: p.Val417Ile, NM&#95;005120.3, was identified. The c.1249G > A variant was validated in the family. Bioinformatic analysis and computational modeling confirmed that c.1249G > A was the pathogenic variant responsible for the DCM phenotype., Conclusion: We detected a novel DCM-causing variant in MED12 using WES. The variant in MED12 may decrease binding to cyclin-dependent kinase 8 (CDK8), affect its activation, and cause alterations in calcium-handling gene expression in the heart, leading to DCM., (© 2023. The Author(s).)

Background: This study aimed to determine the prevalence of glucose metabolism disorder and dyslipidemia in 14-18 year old girls with different phenotype polycystic ovary syndrome (PCOS). Materials and Methods: This descriptive, cross sectional study was conducted on 3200 high school adolescents aged 14-18 years in Shiraz in 2010. Selected parameters of metabolic syndrome (fasting blood glucose, glucose tolerance test [GTT], insulin level, triglyceride (TG), cholesterol, and high density lipoprotein [HDL]), based on adult treatment panel III definition criteria, were compared between the "PCOS" and control groups. Results: Results were compared at four main phenotypes. The level of serum TG was increased in the Phenotype B (P = 0.03) and Phenotype D (P = 0.01), compared to the control group. Cholesterol and low density lipoprotein levels (P < 0.05) and GTT (P > 0.05) were increased, and HDL was decreased (was below 50) in all the four phenotypes and the control group (P > 0.05). Conclusion: The risk of metabolic alterations of glucose metabolism disorder and dyslipidemia in PCOS adolescents was more than non PCOS counterparts. [ABSTRACT FROM AUTHOR]

Aim: Obesity is an emerging public health problem, with its incidence on the rise. An abnormal metabolic profile is a risk factor for developing obesity. Dietary factors play a central role in the regulation of inflammation and obesity. The aim of the present study was to determine the prevalence of metabolically healthy obese and metabolically unhealthy obese (MUO) phenotypes, and their association with dietary inflammatory index (DII) among obese Iranian people. Methods: A cross‐sectional study was conducted from July to October 2017 among 300 obese participants in southern Tehran. DII scores were computed based on the overall inflammatory properties of 32 dietary components using dietary intake assessed by food frequency questionnaire. MUO phenotype was defined as having three or more of these metabolic abnormalities: high blood glucose, high triglycerides, low high‐density lipoprotein cholesterol, elevated blood pressure or abdominal obesity. The association was determined using logistic regression analysis. Results: The MUO phenotype (n = 176) was found in 63.5% of obese participants. Compared with participants in the first quartile, those in the fourth quartile of DII score (more pro‐inflammatory diet) had higher odds of MUO phenotype (odds ratio, OR: 2.58 (95% CI: 1.19–5.59), P = 0.04), and there was a significant association between the continuous form of DII score and the odds of MUO phenotype (OR: 1.18 (95% CI: 1.01–1.37)) after adjusting for potential confounders. Conclusions: Higher DII scores were positively associated with the MUO phenotype. A more pro‐inflammatory diet is a potential risk factor for MUO phenotype. [ABSTRACT FROM AUTHOR]

Previous surveys suggests that body mass index (BMI) may be positively related to development of chronic kidney disease (CKD). However, this association might be altered by metabolic syndrome. Therefore, we aimed to evaluate the association of metabolic health status with CKD. The present cross-sectional study was carried out on 3322 representative sample of Iranian adults. Metabolic syndrome was identified based on the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) and BMI was assessed by anthropometric measurements. Estimated glomerular filtration rate (eGFR) was calculated by modification of diet in renal disease-Chronic Kidney Disease Epidemiology Collaboration (MDRD-EPI) formula. Subjects were categorized into four phenotypes: metabolically healthy normal weight (MHNW), metabolically healthy overweight and obesity (MHO), metabolically unhealthy normal weight (MUHNW), and metabolically unhealthy overweight and obesity (MUHO). Based on multivariate-adjusted models, the risk of CKD was significantly higher in MUHO compared with MHNW (OR: 1.48; p < 0.05). Although MUHNW and MUHO were associated with lower eGFR and albuminuria, the significant association was not observed in case of hematuria. Furthermore, subjects with kidney stones tended to be in MHO (OR: 1.42; p < 0.05) and MUHO phenotypes (OR: 1.64; p < 0.05), in comparison to the MHNW phenotype. The odds of kidney disorders were higher in adults with metabolic syndrome, regardless of BMI. However, this relationship might be strengthened by the concomitance of metabolic syndrome and obesity. To verify our findings, clarify the causality, and elucidate the underlying mechanisms, further research are warranted., (© 2023. The Author(s).)

Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women. This disorder affects 6-15% of women of childbearing age worldwide. It is diagnosed with hyperandrogenism, polycystic ovaries, and chronic anovulation with insulin resistance. This study aimed to assess the prevalence of insulin resistance (IR) in 4 phenotypes of PCOS, and its relationship with demographic, clinical, and paraclinical individual characteristics in a sample of Iranian PCOS patients., Methods: This particular cross-sectional investigation involved 160 female participants, aged between 18 and 45 years, who were receiving care at gynecology clinics in Urmia, northwestern Iran. All the participants had been diagnosed with PCOS and were categorized into one of four phenotypes. All the participants underwent clinical evaluations, paraclinical assessments, and ultrasound scans. IR was defined as HOMA-IR > 2.5. The statistical significance level was 0.05., Results: Among the 160 participants, the prevalences of the 4 phenotypes were: A: 83 (51.9%), B: 37 (23.1%), C: 21 (13.1%), and D: 19 (11.9%). IR was detected in 119 participants (74.4%); its rate was significantly different between the 4 phenotypes (p-value: 0.008) as A: 62 (74.7%), B: 34 (91.9%), C: 12 (57.1%), D: 11 (57.9%). Linear and logistic regression analyses were performed to control confounding factors. In linear regression, PCOS phenotype, classic phenotype (A&B), economic status, and Hb levels were significantly related to HOMA-IR; in logistic regression Hb levels, exercise, economic status, and PCOS phenotypes were significantly associated with insulin resistance., Conclusions: The most prevalent PCOS phenotype in this study was A. PCOS phenotypes were significantly related to insulin resistance and HOMA-IR, with the highest levels of insulin resistance and HOMA-IR observed in phenotype B. Determining the phenotype of PCOS may be helpful for better management of PCOS and its associated complications. However, further investigations are recommended in this regard., (© 2023. The Author(s).)

This study estimated the genetic parameters of productive and reproductive traits of Iranian Holstein cattle from data recorded between 2006 and 2018. The data analysis was performed using animal model, including the record of the first parity and the first three lactation records. Heritability values for milk, fat, and protein using a single record animal model were 0.29 ± 0.005, 0.22 ± 0.005, and 0.24 ± 0.005, respectively. The heritability of these traits based on a repeated model was estimated to be 0.19 ± 0.001, 0.15 ± 0.005, and 0.17 ± 0.006, respectively. Furthermore, the heritability of age at first calving (AFC) and length of lactation (LL) traits were 0.16 ± 0.004 and 0.02 ± 0.002, respectively. Repeatability for milk, fat, and protein yield was 0.38 ± 0.002, 0.34 ± 0.002, and 0.36 ± 0.002, respectively. Positive genetic trend was observed over the years of the study for production traits. Evaluation of the effect of herd-year-season (HYS) on the productive traits revealed that the management and environmental conditions of the farms including feed quality and disease control have been improved. The average heritability for milk, fat, and protein yield and AFC indicates the possibility of genetic improvement for these traits. Furthermore, the repeatability values show that the selection process can be performed based on the first lactation record. The positive genetic trend of productive traits demonstrates the improvement of breeding values in Iranian Holstein cattle., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Genetic variations influence the Von Willebrand Factor plasma level and function. This study aims to evaluate the frequency and clinical phenotype effects of eight single nucleotide polymorphism candidates in four genes (VWF, STXBP5, CLEC4M, and ABO) in Iranian patients with VWD type 1., Method: The study recruited 50 patients with VWD type 1 and 100 healthy individuals. The demographic data from all participants were collected, and the High-Resolution Melting technique was used to determine the frequency of specific single nucleotide polymorphisms. Bleeding scores were also obtained from all patients to assess how these genetic variations might affect the severity of their bleeding symptoms., Results: The study found notable variations in the occurrence of certain SNPs (rs7853989 and rs8176743 for ABO gene and rs1063856 and rs1063857 for VWF gene) between the control group and the patients. Additionally, the study discovered that two SNPs (rs868875 for CLEC4M gene and rs9390459 for STXBP5 gene) were significantly linked to the severity of bleeding, and two others (rs868875 for CLEC4M gene and rs8176746 for ABO gene) were associated with reduced levels of VWF antigen in the patients., Conclusion: According to this study, the above-selected SNPs can cause variations in VWF plasma levels in patients with VWD type 1. Furthermore, the effects of SNPs on bleeding phenotype prove the role of these SNPs in the severity of bleeding manifestations in patients., Competing Interests: Conflict of interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This study aimed to investigate the interaction of the healthy eating index (HEI) and the dietary approach to stop hypertension (DASH) diet scores with FTO polymorphisms in relation to change in obesity traits. A total of 4480 subjects aged ≥ 18 years were selected from participants of the Tehran lipid and glucose study and followed-up 3 years. Selected polymorphisms (rs1421085, rs1121980, rs8050136) were genotyped and genetic risk score (GRS) was computed. HEI and DASH scores were computed based on dietary data. Changes in body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR) and visceral adiposity index (VAI) were measured. Higher adherence to both DASH and HEI scores were increased with higher ages. Individuals with high GRS had a lower change in BMI when they had higher adherence to HEI, compared to subjects with lower HEI score (P trend = 0.01). Change in WC in participants in the fourth quartile of HEI score in minor allele carriers of FTO variants was lower compared to the first quartile; conversely, higher adherence to the DASH score by this genotypic group was related to increase in WC. No significant interaction was seen between FTO polymorphisms and both diet scores regarding changes in any of obesity traits. In conclusion, in individuals with high GRS higher adherence to HEI score was associated with lower change in BMI and WC, while higher adherence to DASH diet was associated with higher change in WC, compared to individuals with lower adherence to both scores., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: It is unknown if the clinical manifestations and phenotype of disease are comparable between early- and elderly-onset inflammatory bowel disease (IBD). We aimed to seek differences in disease phenotype, course, complications, and treatment between early- and elderly-onset IBD patients., Methods: This retrospective cohort study on registered IBD patients in the Iranian Registry of Crohn's and Colitis (IRCC) compared demographics, disease phenotype, disease activity, IBD-related surgery and medications between early- and elderly-onset IBD. A generalized linear regression model was used to investigate the relative risk of age at diagnosis adjusted for gender and disease duration for the outcomes., Results: From 10048 IBD patients, 749 with early-onset (7.5%), and 472 (4.7%) elderly-onset IBD were enrolled: 855 (63.1%) ulcerative colitis (UC) and 366 (26.9%) Crohn's disease (CD). Left-sided colitis was more frequent among elderly-onset UC patients ( P <0.001). Ileum and ileocolonic locations were the most common types in elderly-onset and early-onset CD patients, respectively. In comparison with elderly-onset UC, early-onset cases more often used prednisolone (22.1% vs. 11.4%, P =0.001), immunomodulators (44.9% vs 25.2%, P <0.001) and anti-tumor necrosis factors (TNF) (20.1% vs 11.9%, P =0.002). Elderly-onset UC patients had 0.7 times lower risk of aggressive phenotype (95%CI:0.6‒0.9, P =0.005). Early-onset CD was associated with higher use of prednisolone (27.7% vs 8.1%, P <0.001), immunomodulators (58.7% vs 41.8%, P =0.005) and anti-TNF (49.6% vs 35.4%, P =0.006)., Conclusion: Early-onset IBD was associated with a more aggressive phenotype and higher prednisolone, immunomodulators, and anti-TNF use., (© 2023 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Objective: We aimed to investigate the associations of macronutrient quality indices with the incident metabolically unhealthy normal weight (MUNW) and metabolically unhealthy overweight/obesity (MUO) phenotypes., Methods: This prospective study included 512 metabolically healthy normal weight and 787 metabolically healthy overweight/obese adults from the third study examination of the Tehran Lipid and Glucose Study. The participants were followed through the sixth study examination. Diet was measured with a food frequency questionnaire. The macronutrient quality index (MQI), carbohydrate quality index (CQI), fat quality index (FQI), and healthy plate quality index (HPPQI) were calculated. Hazard ratio (HR) and 95 % confidence interval (95 % CI) were estimated for incident unhealthy phenotypes using Cox regression., Results: After controlling all possible confounding factors, a one-point higher HPPQI was linked to a 28 % lower risk of MUNW (HR = 0.72; 95 % CI = 0.59, 0.87). Compared to the lowest quartile, the incident MUNW was also lower in the two last quartiles of the HPPQI. A one-unit increase in MQI was associated with a 5 % lower incident MUO (HR = 0.95; 95 % CI = 0.92, 0.99). The incident MUO was also higher for the highest compared to the lowest MQI quartile. In quartiles 2-4 of the HPPQI, incident MUO was lower with respective HRs (95 % CI) of 0.71 (0.54, 0.93), 0.60 (0.45, 0.80), and 0.66 (0.50, 0.86) in the fully-adjusted model., Conclusions: A higher overall macronutrient quality was independently associated with a lower incident MUO. A higher dietary protein quality was related to a lower risk for MUNW and MUO., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Pseudomonas syringae pv. syringae (Pss) constitutes a diverse group of bacterial strains that cause canker of stone fruits, blight of cereals and red streak of sugarcane. The purpose of this study was to determine how diverse Iranian strains of Pss are when they come from different hosts. We compared a total of 32 Pss strains isolated from stone fruits, barley, wheat and sugarcane from different geographical regions of Iran based on their phenotypic and molecular properties. Strains showed some variation regarding carbon and nitrogen utilization. Pss strains were similar in their protein banding patterns. Additional bands were found in sugarcane strains. Most strains showed one indigenous plasmid DNA and a few had two and some none. The genes of syrB and syrD encoding syringomycin synthesis and secretion, respectively, were amplified using specific primers in polymerase chain reaction. Syringomycin, producing strains amplified two DNA fragments of 752 and 446 bp representing syrB and syrD genes, respectively. Primer specificity was shown for Pss using various genera. Based on the results of this study, it is suggested that Pss strains from different hosts and geographical regions show diversity in phenotypic and molecular characters. It is thought that phenotypic variation is due to adaptation to specific hosts and niches for survival and pathogenicity. [ABSTRACT FROM AUTHOR]

Background: Cystic Fibrosis (CF) is a life-threatening recessive genetic disorder resulting from mutations in the gene encoding the fibrosis transmembrane conductance regulator protein (CFTR). The CF clinical phenotype shows wide variation ranging from severe disease in early childhood in those homozygous for the p.Phe508del mutation to absence of the vas deferens in otherwise healthy men homozygous for the p.Arg117His mutation. Materials and Methods: DNA was extracted from whole blood from 62 patients with CF. The CFTR mutation was determined by Allele-Specific PCR assay. The spearman and linear regression analysis were used to obtain the correlation between phenotype and genotype relationship. Results: Out of total 62 patients, 35 (56.4%) were male. The mean age of the patients was 15.56 ± 6.65 years. Mutations in CFTR were detected in 64.5% of the patients. The commonest mutations were p.Phe508del (33.9%), p.Arg117His; [5T] (5.64%), p.Arg117His; [7T] (4.03%) and p.Trp1282X (5.64%). Mutations p.Ile507del (4%), p.Gly542X (4%), p.Asn1303Lys (2.42%), c.489+1G>T (1.6%), p.Gly551Asp (1.6%) and c.1585-1G>A (1.6%) were also detected. Most mutations were detected in west and south of Iran, while p.Phe508del mutation was dominant mutation (75%) in east and southeast of Iran. The study showed either an association between this mutation with severity of disease and sex or an association between p.Arg117His mutations and age at diagnosis. Conclusion: The geographic distribution of gene mutation in Iranian cystic fibrosis patients was very heterogenic. In spite of the study that showed a correlation between p.Phe508del and severity of disease, to find any correlation between genotype and phenotype a broad and multi-centered study is recommended. [ABSTRACT FROM AUTHOR]

This study aimed to investigate clinical symptoms in patients with congenital factor V (FV) deficiency and the relationship between phenotype and factor activity level. Thirteen patients with congenital FV deficiency were investigated and the factor activity level and first clinical presentations were studied for each patient. The most common first signs and symptoms were post-surgery, post-partum, post-circumcision, and post-traumatic bleeding (30.76%), followed by easy bruising in 23.10% of the patients. The median age at the onset of clinical signs was 18 (range: 1-53) years. Patients were categorized into two groups of major and minor bleeding based on their first clinical bleeding symptoms. There was not a significant difference between the two groups with regard to factor activity level, age at diagnosis, prothrombin time, partial thromboplastin time, and international normalized ratio (p>0.05). There is a discrepancy between plasma FV activity level and the severity of clinical presentations. [ABSTRACT FROM AUTHOR]