The genetic basis of early-onset hereditary ataxia in Iran: results of a national registry of a heterogeneous population.

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.

Haplotype diversity of 17 Y-STR in the Iranian population.

The current study aimed to evaluate Y chromosome haplotypes obtained from 1353 unrelated Iranian males using the AmpFlSTRTM YfilerTM kit; 1353 out of the 1353 identified haplotypes were unique. The haplotype diversity (HD) and discriminating capacity (DC) values were 1.00000 and 0.997, respectively. Analysis of genetic distance was performed using molecular variance (AMOVA) and multidimensional scaling plots (MDS), revealing a statistically significant difference between the study population and previous data reported for other Iranian populations and other neighboring countries. The present findings are likely to be useful for forensic casework analyses and kinship investigations.

Novel splicing variant and gonadal mosaicism in DYRK1A gene identified by whole-genome sequencing in multiplex autism spectrum disorder families.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with considerable genetic heterogeneity. The disorder is clinically diagnosed based on DSM-5 criteria, featuring deficits in social communication and interaction, along with restricted and repetitive behaviours. Here, we performed whole-genome sequencing (WGS) on four individuals with ASD from two multiplex families (MPX), where more than one individual is affected, to identify potential single nucleotide variants (SNVs) and structural variants (SVs) in coding and non-coding regions. A rigorous bioinformatics pipeline was employed for variant detection, followed by segregation analysis. Our investigation revealed an unreported splicing variant in the DYRK1A gene (c.-77 + 2T > C; IVS1 + 2T > C; NM_001396.5), in heterozygote form in two affected children in one of the families (family B), which was absent in the healthy parents and siblings. This finding suggests the presence of gonadal mosaicism in one of the parents, representing the first documented instance of such inheritance for a variant in the DYRK1A gene associated with ASD. Furthermore, we identified a 50 bp deletion in intron 9 of the DLG2 gene in two affected patients from the same family, confirmed by PCR and Sanger sequencing. In Family A, we identified potential candidate variants associated with ASD shared by the two patients. These findings enhance our understanding of the genetic landscape of ASD, particularly in MPX families, and highlight the utility of WGS in uncovering novel genetic contributions to neurodevelopmental disorders.

Pro-vegetarian dietary pattern and risk of breast cancer: a case-control study.

BACKGROUND: There are a few conflicting results from studies assessing the association between plant-based diets, particularly pro-vegetarian dietary pattern (PDP), and breast cancer (BC) incidence. Therefore, this study aimed to investigate the association between PDP and BC odds in the Iranian population. METHODS: This case-control study was conducted on 134 women with BC and 265 without cancer (control). Participants were selected from two referral hospitals in Tehran, Iran. Also, a validated food frequency questionnaire was used to collect food information. Logistic regression was used to assess the association between PDP and BC and the association between PDP and BC by menopausal status. RESULTS: It was observed that in two models of logistic regression, the chance of BC was lower in the second and last tertile (T) than in the first tertile of PDP (model 1-T2: odds ratio (OR) = 0.39; 95% confidence interval (CI): 0.23-0.67; P = 0.001, and T3: OR = 0.43; 95% CI: 0.26-0.73; P = 0.002-model 2: T2: OR = 0.42; 95% CI: 0.24-0.74; P = 0.003, and T3: OR = 0.49; 95% CI: 0.27-0.88; P = 0.017). Also, according to menopausal status, the odds of developing BC in post-menopausal women in the second and last tertile of PDP was significantly lower than the first tertile in both logistic regression models. CONCLUSIONS: The findings revealed that Iranian women who followed PDP had a lower chance of developing BC. Also, we found that a diet high in plant-based foods and low in animal products is beneficial for reducing BC odds, particularly for post-menopausal women.

Measurement properties of the Iranian version of the breast cancer perception scale (BCPS) according to the COSMIN checklist.

BACKGROUND: Breast cancer is a prevalent cancer characterized by its aggressive nature and potential to cause mortality among women. The rising mortality rates and women's inadequate perception of the disease's severity in developing countries highlight the importance of screening using conventional methods and reliable scales. Since the validity and reliability of the breast cancer perception scale (BCPS) have not been established in the Iranian context. Therefore, this study aimed to determine the measurement properties of the BCPS in women residing in Tabriz, Iran. METHODS: The present study comprised a cross-sectional design, encompassing a sample of 372 Iranian women. The participants were selected through a multi-stage cluster random sampling technique conducted over a period spanning from November 2022 to February 2023. The measurement properties of the Iranian version of BCPS were assessed following the guidelines outlined in the COSMIN checklist. This involved conducting various steps, including the translation process, reliability testing (internal consistency, test-retest reliability, and measurement error), and methodological tests for validity (content validity, face validity, construct validity, and hypothesis testing). The study also investigated the factors of responsiveness and interpretability. The presence of floor and ceiling effects was assessed. RESULTS: The internal consistency of the scale was assessed using Cronbach's alpha, yielding a satisfactory value of 0.68. Additionally, McDonald's omega (95% CI) was computed, resulting in a value of 0.70 (0.66 to 0.74). Furthermore, the test-retest reliability was evaluated, revealing a high intraclass correlation coefficient (ICC) of 0.97 (95% CI: 0.94 to 0.99). The CVI, CVR, and impact scores of the BCPS were determined to be 0.98, 0.95, and 3.70, respectively, indicating favorable levels of content and face validity. To assess construct validity, an examination of the Exploratory Factor Analysis (EFA) was conducted on a set of 24 items. This analysis revealed the presence of six distinct factors, which collectively accounted for 52% of the cumulative variance. The fit indices of the validity model (CFI = 0.91, NFI = 0.96, RFI = 0.94, TLI = 0.90, χ2/df = 2.03, RMSEA = 0.055 and SRMR = 0.055) were confirmed during the confirmatory factor analysis (CFA). The overall score of BCPS exhibited a ceiling effect of 0.3%. The floor effect observed in the overall score (BCPS) was found to be 0.5%. Concerning the validation of the hypothesis, Spearman's correlation coefficient of 0.55 was obtained between the BCPS and the QLICP-BR V2.0. This correlation value signifies a statistically significant association. Furthermore, it is worth noting that the minimum important change (MIC) of 3.92 exhibited a higher value compared to the smallest detectable change (SDC) of 3.70, thus suggesting a satisfactory level of response. CONCLUSIONS: The obtained findings suggest that the Iranian version of the BCPS demonstrates satisfactory psychometric properties for assessing the perception of breast cancer among Iranian women. Furthermore, it exhibits favorable responsiveness to clinical variations. Consequently, it can serve as a screening instrument for healthcare professionals to comprehend breast cancer and as a reliable tool in research endeavors.

Comparison of the long-term and short-term protection in mouse model of Leishmania major infection following vaccination with Live Iranian Lizard Leishmania mixed with chitin microparticles.

Inducing long-term immunity is the primary goal of vaccination. Leishmanisation using non-pathogenic to human Leishmania spp. could be considered a reliable approach to immunising subjects against Leishmania infection. Here, we evaluated the long-term immune responses (14 weeks) after immunisation with either live- or killed-Iranian Lizard Leishmania (ILL) mixed with chitin microparticles (CMPs) against L. major infection in BALB/c mice. In total, nine groups of mice were included in the study. To evaluate short-term immunity, mice were immunised with live-ILL and CMPs and 3 weeks later were challenged with L. majorEGFP . To evaluate the long-term immunity, mice were immunised with either live- or killed-ILL both mixed with CMPs, and 14 weeks after immunisation, mice were challenged with L. majorEGFP . A group of healthy mice who received no injection was also included in the study. Eight weeks after the challenge with L. majorEGFP , all subjects were sacrificed and the parasite burden (quantitative real-time PCR and in vivo imaging), cytokines levels (IFN-γ, IL-4 and IL-10), Leishmania-specific antibody concentration, and total levels of IgG1 and IgG2a were measured. In addition, nitric oxide concentration and arginase activity were evaluated. Results showed that in mice that were immunised using live-ILL+CMP, the induced protective immune response lasted at least 14 weeks; since they were challenged with L. majorEGFP at the 14th -week post-immunisation, no open lesion was formed during the 8-week follow-up, and the footpad swelling was significantly lower than controls. They also showed a significant reduction in the parasite burden in splenocytes, compared to the control groups including the group that received killed-ILL+CMP. The observed protection was associated with a higher IFN-γ and a lower IL-10 production by splenocytes. Additionally, the results demonstrated that arginase activity was decreased in the ILL+CMP group compared to other groups. Immunisation with ILL alone reduced the parasite burden compared to non-immunised control; however, it was still significantly higher than the parasite burden in the ILL+CMP groups. In conclusion, the long-term immune response against L. major infection induced by Live-ILL+CMP was more competent than the response elicited by killed-ILL+CMP to protect mice against infection with L. majorEGFP .

Genetic diversity and positive signatures of selection in indigenous cattle breeds of Iran.

Animal domestication, climate changes over time, and artificial selection have played significant roles in shaping the genome structure of various animal species, including cattle. These processes have led to the emergence of several indigenous cattle breeds with distinct genetic characteristics. This study focused on unraveling the genetic diversity and identifying candidate genomic regions in eight indigenous cattle breeds of Iran. The data consisted of ∼777 962 single nucleotide polymorphisms (SNPs) of 89 animals from Iranian indigenous cattle scattered throughout the country. We employed various methods, including integrated haplotype score, FST, and cross-population composite likelihood ratio, to conduct a genome scan for detecting selection signals within and between cattle populations. Average observed heterozygosity across the populations was 0.36, with a range of 0.32-0.40. In addition, negative and low rates of inbreeding (FIS) in the populations were observed. The genome-wide analysis revealed several genomic regions that harbored candidate genes associated with production traits (e.g., MFSD1, TYW5, ADRB2, BLK, and CRTC3), adaptation to local environmental constraints (CACNA2D1, CXCL3, and GRO1), and coat color (DYM). Finally, the study of the reported quantitative trait loci (QTL) regions in the cattle genome demonstrated that the identified regions were associated with QTL related to important traits such as milk composition, body weight, daily gain, feed conversion, and residual feed intake. Overall, this study contributes to a better understanding of the genetic diversity and potential candidate genes underlying important traits in Iranian indigenous cattle breeds, which can inform future breeding and conservation efforts.

Exploring the understanding and experience of women with rheumatic diseases regarding fertility intention- a qualitative content analysis.

BACKGROUND: Patients with rheumatic diseases (RDs) have a lower desire to have children, fewer children, and a longer interval between their pregnancies, which can be due to the patient's personal choice, the physician's advice, changes in sexual activity, changes in fertility, and pregnancy failure. This study aimed to explore the understanding and experience of women with RDs regarding pregnancy intention. METHOD: In Mashhad, Northeast Iran, between December 2022 and March 2023, this qualitative inquiry was carried out. Purposive sampling was used to select thirty women with RDs. Semi-structured interviews were used to collect the data. Graneheim and Lundman's conventional content analysis method was used to analyze the data. The data organization was done using MAXQDA 12 software. Credibility, dependability, confirmability, and transferability have been considered as elements of trustworthiness. RESULTS: The participants' data analysis revealed the following main theme: "duality of desire and fear in childbearing". Five main categories were identified, including "Individual health concerns following pregnancy", "motherhood and womanhood perceptions", "concerns about child harm", "contradictory beliefs and attitudes of significant family members and clinicians about pregnancy", and "lack of social support for fertility". CONCLUSION: In order to improve the outcomes of pregnancy for women with RDs, the medical professionals who manage them must actively and frequently inquire about their intentions to childbearing and offer them individualized guidance on how to be in the best possible health at the time of conception. Rheumatologists, gynecologists, and reproductive health specialists can better address the sexual and reproductive health needs of this population by enhancing their collaboration in the care of women with RDs.

The association between healthy beverage index and sarcopenia in Iranian older adults: a case-control study.

BACKGROUND: Sarcopenia is a progressive disease with age-related loss of skeletal muscle mass, strength, and function. No study has investigated the association between healthy beverage index (HBI) and sarcopenia in older adults. Therefore, the present study aimed to investigate the association between HBI and sarcopenia in Iranian older adults. METHODS: In the present case-control study, 80 sarcopenic and 80 non-sarcopenic participants matched in sex were included. Body composition was measured using bioelectrical impedance analysis. Handgrip strength (HGS), skeletal muscle mass index (SMI), and gait speed were utilized to confirm sarcopenia. Also, a food frequency questionnaire was used to evaluate food intake. HBI score was calculated based on ten sub-components of the total beverages. Moreover, logistic regression was applied to assess the association between HBI and sarcopenia. RESULTS: In the crude model, we observed no significant association between HBI and the odds of sarcopenia. Still, after adjusting the confounders, the odds of developing sarcopenia decreased significantly in the second and last tertiles (T) (T2- odds ratio (OR) = 0.04, 95% confidence interval (CI): 0.01-0.25 and T3- OR = 0.10, 95% CI: 0.01-0.60). CONCLUSIONS: Our findings indicated that HBI is inversely related to the chance of sarcopenia. Therefore, to reduce the odds of sarcopenia, it is recommended to consume healthy drinks such as fruit juices and milk.

Gene network modeling and pathway analysis of maize transcriptomes in response to Maize Iranian mosaic virus.

Maize Iranian mosaic virus (MIMV, family Rhabdoviridae) is one of the factors limiting cereal production in Iran. In the present study, we sought to find critical genes and key pathways involved in MIMV infection and analyzed gene networks, pathways and promoters using transcriptome data. We determined the hub genes involved in pathways related to the proteasome and ubiquitin. The results showed the important role of the cellular endoplasmic reticulum in MIMV infection. Network cluster analysis confirmed the result of GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The discovered miRNAs belonged to miR166, miR167, miR169, miR395, miR399, miR408 and miR482 families, which are involved in various pathogenicity or resistance processes against MIMV or other viruses. The results of this study provide a list of hub genes, important pathways and new insights for the future development of virus-resistant transgenic crops and clarify the basic mechanism of plant response.

Challenges facing international students at Iranian universities: a cross-sectional survey.

BACKGROUND: This study examines the challenges faced by international students at Tehran University of Medical Sciences (TUMS) and provides insights into their experiences and needs. METHODOLOGY: A self-developed structured questionnaire was administered to international students who completed their first year at TUMS. Data were collected from 165 participants (76% response rate) and analyzed using SPSS 22.0. RESULTS: The study reveals that international students encounter various challenges, including difficulties accessing information, language barriers, ineffective communication, administrative inefficiencies, cultural issues, financial constraints, and limited scholarship opportunities. Analysis of students' characteristics indicates that the length of study at TUMS is significantly associated with the challenges experienced. The findings highlight the importance of enhancing support services and resources for international students, such as language classes, academic counseling, scholarships, and cultural exchange programs. CONCLUSION: Addressing these challenges can foster a more supportive environment, contributing to the academic success and well-being of international students at TUMS and similar universities.

Predictive factors of occupational stress among nurses during the COVID-19 pandemic: a cross-sectional study in Kashan, Iran.

BACKGROUND: Considering the severe and sudden changes in the job conditions of nurses during the covid-19 pandemic, the increase in job tensions during this critical period and its consequences on the quantity and quality of nursing care, this study aims to investigate the job stress of nurses during the covid-19 pandemic and its predictors in Iran. METHODS: This cross-sectional study was conducted on 400 nurses in 'Kashan', Iran, who were randomly selected using stratified sampling. Data were collected using two questionnaires on occupational stress and potential related factors. The data were analyzed in SPSS version 16. RESULTS: The results showed that the occupational stress of nurses in Iran was at a medium to high level with a mean and standard deviation of 103.773 ± 15.742 (scale of 34-136). Factors such as satisfaction with physical health, quality of work life, satisfaction with the availability of facilities, sense of coherence, education level, work experience, job burnout, male gender, being native, and workplace were predictors of occupational stress and explained 23.3% of the variance in occupational stress score. The highest contribution was related to satisfaction with physical health. CONCLUSION: Considering the consequences of occupational stress for nurses, it is crucial for health and nursing authorities to take these factors into consideration in policy-making and planning.

Exploring the Nature of Near-Death Experiences in Iranian Experiencers: A Case Study of the Participants in the Life after Life TV Series.

Near-death experiences (NDEs) are complex and challenging. The development of research on NDEs helps to understand and recognize this complex human phenomenon more effectively. The present study sought to explore the nature of NDEs in the lived experiences of Iranian who experienced near-death incidents (NDErs) using a qualitative phenomenological approach. The participants were 34 persons selected from Iranian NDErs. The collected data were analyzed using Colaizzi's seven-step content analysis with MAXQDA software (version 2021). The data revealed 11 semantic codes about the nature of NDEs reported by Iranian NDErs. Overall, the results showed that the components of NDEs in many cases are similar to the nature of NDEs of the world. However, the type and quality of the positive and negative NDEs reported by Iranian people are different in terms of the feedback of actions and the return to the body compared to other NDEs reported by people in other countries.

The frequency of NRAS mutation in stool samples of Iranian colorectal cancers compared to Finnish patients.

Background: Stools from colorectal cancer patients are noninvasive samples that could be used to compare the frequency of hotspot mutations between two different ethnic cohorts. Materials and Methods: We collected stool samples from the Iranian cohort (52 patients and 49 controls) and the Finnish cohort (40 patients and 14 controls). Following stool DNA extraction, we used the AmpliSeq Colon and Lung Cancer panel to prepare DNA libraries before sequencing. Results: The Iranian cohort exhibited 35 hotspot mutations in the BRAF, ERBB4, FBXW7, FGFR1, FGFR3, KRAS, MAP2K, MET, NRAS, PIK3C, SMAD4, and TP53 genes. In the Finnish cohort, 13 hotspot mutations were found in the AKT1, APC, KIT, KRAS, SMO, STK11, and TP53 genes. Mutations in NRAS and FGFR3 were observed only in the Iranian cohort, while APC mutations were exclusive for the Finnish cohort. Conclusion: Genes involved in MAPK and PI3K-MAPK pathways showed a higher frequency of mutations in Iranian patients which may have therapeutic implications.

Mutational landscape of phenylketonuria in Iran.

To date more than 1000 different variants in the PAH gene have been identified in patients with phenylketonuria (PKU). In Iran, several studies have been performed to investigate the genetics bases of the PKU in different parts of the country. In this study, we have analysed and present an update of the mutational landscape of the PAH gene as well as the population genetics and frequencies of detected variants for each cohort. Published articles on PKU mutations in Iran were identified through a comprehensive PubMed, Google Scholar, Web of Science (ISI), SCOPUS, Elsevier, Wiley Online Library and SID literature search using the terms: "phenylketonuria", "hyperphenylalaninemia", and "PKU" in combination with "Iran", "Iranian population", "mutation analysis", and "Molecular genetics". Among the literature-related to genetics of PKU, 18 studies were on the PKU mutations. According to these studies, in different populations of Iran 1497 patients were included for mutation detection that resulted in detection of 129 different mutations. Results of genetic analysis of the different cohorts of Iranian PKU patients show that the most prevalent mutation in Iran is the pathogenic splice variant c.1066-11G > A, occurring in 19.54% of alleles in the cohort. Four other common mutations were p.Arg261Gln, p.Pro281Leu, c.168 + 5G > C and p.Arg243Ter (8.18%, 6.45%, 5.88% and 3.7%, respectively). One notable feature of the studied populations is its high rate of consanguineous marriages. Considering this feature, determining the prevalent PKU mutations could be advantageous for designing screening and diagnostic panels in Iran.

COLQ-related congenital myasthenic syndrome: An integrative view.

Congenital myasthenic syndromes are inherited disorders caused by mutation in components of the neuromuscular junction and manifest early in life. Mutations in COLQ gene result in congenital myasthenic syndrome. Here, we present the analysis of data from 209 patients from 195 unrelated families highlighting genotype-phenotype correlation. In addition, we describe a COLQ homozygous variant a new patient and discuss it utilizing the Phyre2 and I-TASSER programs. Clinical, molecular genetics, imaging (MRI), and electrodiagnostic (EEG, EMG/NCS) evaluations were performed. Our data showed 89 pathogenic/likely pathogenic variants including 35 missenses, 21 indels, 14 nonsense, 14 splicing, and 5 large deletions variants. Eight common variants were responsible for 48.46% of those. Weakness in proximal muscles, hypotonia, and generalized weakness were detected in all individuals tested. Apart from the weakness, extensive clinical heterogeneity was noted among patients with COLQ-related patients based on their genotypes-those with variants affecting the splice site exhibited more severe clinical features while those with missense variants displayed milder phenotypes, suggesting the role of differential splice variants in multiple functions within the muscle. Analyses and descriptions of these COLQ variants may be helpful in clinical trial readiness and potential development of novel therapies in the setting of established structure-function relationships.

Unravelling the genetic diversity and population structure of common walnut in the Iranian Plateau.

BACKGROUND: Common walnut (Juglans regia L.) has a long cultivation history, given its highly valuable wood and rich nutritious nuts. The Iranian Plateau has been considered as one of the last glaciation refugia and a centre of origin and domestication for the common walnut. However, a prerequisite to conserve or utilize the genetic resources of J. regia in the plateau is a comprehensive evaluation of the genetic diversity that is conspicuously lacking. In this regard, we used 31 polymorphic simple sequence repeat (SSR) markers to delineate the genetic variation and population structure of 508 J. regia individuals among 27 populations from the Iranian Plateau. RESULTS: The SSR markers expressed a high level of genetic diversity (HO = 0.438, and HE = 0.437). Genetic differentiation among the populations was moderate (FST = 0.124), and genetic variation within the populations (79%) significantly surpassed among populations (21%). The gene flow (Nm = 1.840) may have remarkably influenced the population genetic structure of J. regia, which can be attributed to anthropological activities and wind dispersal of pollen. The STRUCTURE analysis divided the 27 populations into two main clusters. Comparing the neighbor-joining and principal coordinate analysis dendrograms and the Bayesian STRUCTURE analysis revealed the general agreement between the population subdivisions and the genetic relationships among the populations. However, a few geographically close populations dispersed into different clusters. Further, the low genetic diversity of the Sulaymaniyah (SMR) population of Iraq necessitates urgent conservation by propagation and seedling management or tissue culture methods; additionally, we recommend the indispensable preservation of the Gonabad (RGR) and Arak (AKR) populations in Iran. CONCLUSIONS: These results reflected consistent high geographical affinity of the accession across the plateau. Our findings suggest that gene flow is a driving factor influencing the genetic structure of J. regia populations, whereas ecological and geological variables did not act as strong barriers. Moreover, the data reported herein provide new insights into the population structure of J. regia germplasm, which will help conserve genetic resources for the future, hence improving walnut breeding programs' efficiency.

Two fluorimetric determinations of acid α-glucosidase activity in dried blood spot: Pompe disease in Iranian population.

INTRODUCTION: Pompe disease is a lysosomal storage disorder. This study aimed to validate and compare 2 fluorimetric methods for measuring α-glucosidase acid activity in dried blood spot sample (DBS), with potential applications in neonatal screening, and disease follow-up of Pompe patients among the Iranian population for the first time. MATERIALS AND METHODS: The evaluation involved 3 enzyme levels and 7 parameters. The analysis included 141 Healthy individuals, 8 Pompe patients, and 10 obligate heterozygotes using reference and modified methods. RESULTS: Both methods exhibited highly linear calibration curves. The limit of detection (LOD) and limit of quantification (LOQ) were obtained in the micromolar concentration range in 2 methods. Inter-day and intra-day precision, expressed as relative standard deviations (RSD%) were calculated. The normal ranges were determined in healthy individuals. Receiver operating characteristic (ROC) curves were analyzed, and 2 parameters, total neutral α-glucosidase (NAG)/acid α-glucosidase (GAA) and pH ratio, were identified as cut-off values with excellent accuracy, sensitivity, and specificity for evaluating Pompe disease in both methods. CONCLUSIONS: Establishing and implementing these 2 methods for the Iranian population effectively differentiated between healthy and patient individuals. Method II, with its shorter incubation time, demonstrated practicality in the clinical setting.

Dietary and lifestyle indices for hyperinsulinemia and colorectal cancer risk: a case-control study.

BACKGROUND: The incidence of colorectal cancer (CRC) has increased in Iran, and determining the dietary patterns that can contribute to reducing or increasing the risk of CRC will help better control this disease. Therefore, in the current study, we assessed the association between the empirical lifestyle index for hyperinsulinemia (ELIH) and the empirical dietary index for hyperinsulinemia (EDIH) with the CRC odds. METHODS: The present case (n = 71)-control (n = 142) study was carried out in several CRC surgical units of hospitals in Tehran, Iran. A semi-quantitative food frequency questionnaire containing 168 items was used to assess participants' dietary intakes. The EDIH and ELIH scores were calculated by food groups and some variables such as body mass index and physical activity. Logistic regression models were applied to evaluate the association between the EDIH and ELIH scores with CRC odds. RESULTS: According to baseline features of the study participants, there were significant differences between the controls and cases in ELIH score, fiber intake, taking aspirin, and family history of CRC in first- and second-degree relatives. Also, we found that the odds of CRC increased significantly in the last tertile compared to the first tertile in EDIH and ELIH in the adjusted model (odds ratio (OR) = 3.12; 95% confidence interval (CI): 1.30-7.48 and OR = 4.72; 95% CI: 1.15-19.39, respectively). CONCLUSIONS: In conclusion, the result of this study indicated that CRC odds was significantly greater in subjects with higher EDIH and ELIH scores. Also, according to the results of this study, lifestyle and diet with insulinemic potential can influence the CRC risk.

Reporting a novel growth hormone receptor gene variant in an Iranian consanguineous pedigree with Laron syndrome: a case report.

BACKGROUND: Human growth hormone (hGH) plays a crucial role in growth by binding to growth hormone receptor (GHR) in target cells. Binding of GH molecules to their cognate receptors triggers downstream signaling pathways leading to the transcription of several genes, including insulin-like growth factor (IGF)-1. Pathogenic variants in the GHR gene can result in structural and functional defects in the GHR protein, leading to Laron Syndrome (LS) with the primary clinical manifestation of short stature. So far, around 100 GHR variants have been reported, mostly biallelic, as causing LS. CASE PRESENTATION: We report on three siblings from an Iranian consanguineous family who presented with dwarfism. Whole-exome sequencing (WES) was performed on the proband, revealing a novel homozygous missense variant in the GHR gene (NM_000163.5; c.610 T > A, p.(Trp204Arg)) classified as a likely pathogenic variant according to the recommendation of the American College of Medical Genetics (ACMG). Co-segregation analysis was investigated using Sanger sequencing. CONCLUSIONS: To date, approximately 400-500 LS cases with GHR biallelic variants, out of them 10 patients originating from Iran, have been described in the literature. Given the high rate of consanguineous marriages in the Iranian population, the frequency of LS is expected to be higher, which might be explained by undiagnosed cases. Early diagnosis of LS is very important, as treatment is available for this condition.