Hepatitis C infection seroprevalence in pregnant women worldwide: a systematic review and meta-analysis.

Background: Monitoring progress towards the WHO global target to eliminate hepatitis C virus (HCV) infection by 2030, entails reliable prevalence estimates for HCV infection in different populations. Little is known about the global burden of HCV infection in pregnant women. Here, for the first time to our knowledge, we estimated the global and regional seroprevalence of HCV antibody (Ab) and determinants in pregnant women. Methods: In this systematic review and meta-analysis study, we searched PubMed/MEDLINE, Web of Science, Embase, Scopus, and SciELO databases for peer-reviewed observational studies between January 1, 2000 and April 1, 2023, without language or geographical restrictions. Pooled global seroprevalence (and 95% confidence interval, CI) were estimated using random-effects meta-analysis and seroprevalences were categorised according to World Health Organization regions and subregions, publishing year, countries' income and human development index (HDI) levels. We used sensitivity analysis to assess the effect of four large sample size studies on pooled global prevalence through the "leave-one-out" method. We also investigated the association of potential risk factors with HCV seropositivity in pregnant women by subgroup and meta-regression analyses. The Protocol was registered in PROSPERO CRD42023423259. Findings: We included 192 eligible studies (208 datasets), with data for 148,509,760 pregnant women from 53 countries. The global seroprevalence of HCV Ab in pregnant women was 1.80% (95% CI, 1.72-1.89%) and 3.29% (3.01-3.57%) in overall and sensitivity analyses, respectively. The seroprevalence was highest in the Eastern Mediterranean region (6.21%, 4.39-8.29%) and lowest in the Western Pacific region (0.75%, 0.38-1.22%). Subgroup analysis indicated that the seroprevalence of HCV Ab among pregnant women was significantly higher for those with opioid use disorder (51.94%, 95% CI: 37.32-66.39) and HIV infection (4.34%, 95% CI: 2.21-7.06%) than for the general population of pregnant women (1.08%, 95% CI: 1.02-1.15%), as confirmed by multivariable meta-regression (p < 0.001). A significant decreasing trend was observed with increasing human development index levels. Other important risk factors for HCV seropositivity included older age, lower educational levels, poly sexual activity, history of blood transfusion, hospitalization, surgery, abortion and sexual transmitted diseases, having scarification/tattoo or piercing, and testing hepatitis B positive. Interpretation: This meta-analysis showed relatively high burden of exposure to HCV infection (2.2-5.3 million) in pregnant women globally. However, due to substantial heterogeneity between studies, our estimates might be different than the true seroprevalence. Our findings highlighted the need to expand HCV screening for women of reproductive age or during pregnancy, particularly in countries with high prevalence; as well as for more studies that assess safety of existing therapeutic drugs during pregnancy or potentially support development of drugs for pregnant women. Funding: There was no funding source for this study.

Chlamydia pneumonia infection and risk of multiple sclerosis: A meta-analysis.

BACKGROUND: The role of infectious agents, including Chlamydia pneumoniae (Cpn), in the development of multiple sclerosis (MS), is still a matter of major contention. OBJECTIVE: This meta-analysis study aimed to assess the actual involvement of Cpn in MS development. METHODS: We undertook a search of international scientific databases to identify eligible studies. We used a random-effects meta-analysis model (REM) to generate the pooled odds ratio (OR) and 95% confidence intervals (CIs). Heterogeneity was calculated using the I2 statistic. Sensitivity and subgroup analyses were applied to assess the effects of study characteristics and socio-demographic variables on the pooled OR. RESULTS: We identified 37 studies comprising 51 datasets that satisfied the inclusion criteria. Considering diagnostic methods for Cpn, 26 and 25 datasets used PCR- and serological-based methods, respectively. In PCR-based datasets, REM showed a significant positive association between Cpn infection and the development of MS (OR, 5.29; 95% CI, 3.12-8.97), while a non-significant positive association was achieved in serological-based datasets (OR, 1.34; 95% CI, 0.88-2.03). In subgroup analyses on PCR-based datasets, results were significant for both CSF (OR, 5.70) and serum (OR, 4.84) samples; both healthy (OR, 16.11) and hospital-based (OR, 2.88) controls; and both moderate (OR, 5.14) and high (OR, 5.48) quality studies. In serological-based datasets, only those that used CSF samples yielded significant results (OR, 3.41). CONCLUSIONS: Our findings verify the significant positive relationship between Cpn infection and MS. We advocate prospective cohort studies with lifelong follow-ups and also experimental studies to better understand the role of Cpn in MS development.

Dysregulation of PVT1 and NEAT1 lncRNAs in pituitary adenomas.

Pituitary adenomas are slow-growing tumors originated from the anterior part of pituitary gland. These tumors are associated with dysregulation of a number of long non-coding RNAs (lncRNAs). PVT1, TUG1, MALAT1, NEAT1 and GAS5 are among lncRNAs with important roles in the regulation of cell proliferation, cell apoptosis, cell differentiation and cell cycle transition. In the current study, we assessed expression levels of PVT1, TUG1, MALAT1, NEAT1 and GAS5 in the pituitary adenoma samples compared with adjacent non-cancerous samples to find their relevance with this type of tumors and their potential as diagnostic markers in these tumors. Expression of NEAT1 was significantly higher in total adenoma tissues (Expression ratio (95% CI)= 7.06 (2.31-21.4), P value= 0.02) and in non-functioning pituitary adenoma (NFPA) samples (Expression ratio (95% CI)= 8.5 (2.17-33.12), P value= 0.04) compared with corresponding controls. Although both lncRNAs had appropriate sensitivity values for discrimination of NFPAs from adjacent non-cancerous tissues (0.84 and 0.90 for PVT1 and NEAT1, respectively), the calculated AUC values were not adequate for either lncRNAs (0.63 ± 0.04 and 0.58 ± 0.04 for PVT1 and NEAT1, respectively). Therefore, NEAT1 and PVT1 lncRNAs are dysregulated in NFPA. The current study suggests the role of NEAT1 and PVT1 in the pathogenesis of NFPA.

Determination of Bone Density by DEXA Method Based on Bone Age and its Comparison with Chronological Age in Chronic Patients.

Background and Objective: Given the growing awareness about the important role of children's age in building bone for a person's life, physicians need to assess bone health in high-risk children for bone density disorders more than before to optimize their bones' density and prevent osteoporosis in future. The aim of this study was to evaluate bone density based on chronological and bone age. Materials and Methods: In this cross-sectional study, 80 Patients who have been referred for bone density to the Osteoporosis Centre of the Children's Medical Centre over a one-year period (spring 98 to spring 99) were studied. Bone density was performed for all patients by using DEXA method. Results: The z-score mean chronological age for the lumbar spine was -0.8± 1.85 years and bone age was -0.58±1.64 years. The z-score mean chronological age for femoral bone was -1.6±1.02 years and bone age was -1.32± 1.4 years. Conclusion: Results showed that in all patients, the difference in the mean Z score of chronological age and bone age of the spine between patients was not significant but for femur was significant. Also, use of corticosteroids leads to significant difference between the two age groups' z-score in femur and spine.

Relationship between a near Melanocortin-4 receptor gene variant and puberty timing in children is vague unlike obesity.

Background: Obesity is a complicated phenomenon which is a combination of genetic, environmental, and psychological factors. Genetic factors of obesity play an important role in individual risk. It is well known that obese children have disturbed puberty timing. To the best of our knowledge, no study has been performed to investigate the association between MC4R gene mutation and puberty timing. Methods: This study was performed as a cross-sectional study evaluating the near MC4R rs17782313 variation in 60 obese children and 98 healthy non obese children. Weight, height, BMI ( Body Mass Index ), BMI z-score (BMIz), family history of diabetes mellitus and obesity, the age of the obesity onset, overeating behavior, type of obesity (central or general) and puberty stage were evaluated in 60 obese children. Results: The average age of the participants was 14.87 (+/- 1.3) years, with average weight and BMI of 90.77 (+/-12.2) Kg and 31.72 (+/-4.35) Kg/m2, respectively. Compared to healthy non obese patients, those with C-T genotype (C-T Vs. T-T and C-C) had higher odds of obesity than those with T-T and C-C genotype (p < 0.0001) while genotype TT showed significant protective effect (p = 0.0007). The heterozygote individuals (CT) have a higher BMIz than homozygote ones (CC and TT) (2.8 vs. 2.5 Kg/m2, p = 0.04). Conclusions: children with CT genotype have 5.1 increased risk of obesity. While genotype TT showed significant obesity protective effect. We did not find association of this polymorphism with either childhood eating disorders or puberty. It is recommended to perform a cohort study in a larger sample. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-01011-5.

Mesenchymal stem cell transplantation in newly diagnosed type-1 diabetes patients: a phase I/II randomized placebo-controlled clinical trial.

BACKGROUND: Type-1 diabetes (T1D) occurs following autoimmune-induced pancreatic beta cells death. Among several treatment modalities, mesenchymal stem cells (MSCs) transplantation is promising for autoimmune disorders due to immunomodulation, regeneration, and migration to damaged tissue upon systemic injection. This study assessed the safety and efficacy of intravenous injection of autologous bone marrow-derived MSCs in newly diagnosed T1D patients. METHODS: After receiving informed consent, 21 patients who met the study criteria were enrolled and randomly assigned to receive either MSCs or placebo. Each patient in the experimental group received two doses of MSCs and was followed for at least one-year post-transplantation. RESULTS: The results have shown that this transplantation is safe and significantly reduces the number of hypoglycemic episodes. MSCs transplantation improved glycated hemoglobin (HbA1c), shifted serum cytokine patterns from pro-inflammatory to anti-inflammatory, increased the number of regulatory T-cells in the peripheral blood, and improved quality of life. Early transplantation of MSCs significantly improved HbA1c and C-peptide levels and shifted pro-inflammatory cytokines to anti-inflammatory cytokines. Also, exercise combined with MSCs transplantation improved glycemic and immunologic indices. CONCLUSIONS: Taken together, autologous MSC transplantation is safe and effective, and its early transplantation is a promising treatment in newly diagnosed T1D children suffering from hypoglycemic episodes. TRIAL REGISTRATION: This clinical trial was registered at the Iranian Registry of Clinical Trials (IRCT) with the identifier IRCT ID: IRCT2016070428786N1 registered on August 20, 2016 (Retrospectively registered) ( https://en.irct.ir/trial/23256 ) and at the U.S. National Institutes of Health (ClinicalTrials.gov) with the related identifier NCT04078308 registered on September 6, 2019 (Retrospectively registered). ( https://clinicaltrials.gov/ct2/show/NCT04078308 ).

Molecular and clinical characterization of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) in Iranian non-Jewish patients: report of two novel AIRE gene pathogenic variants.

OBJECTIVE: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) is a rare autosomal recessive systemic autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene. Incidence of this genetic disorder is estimated at 1/90,000-200,000 worldwide and 1/6500-9000 in genetically isolated populations such as Iran. Here, we investigated AIRE gene mutations in eight independent Iranian non-Jewish families. METHODS: We sequenced the coding regions of the AIRE gene and documented mutations which were further confirmed in respective parents. RESULTS: In total, 11 cases from 8 independent families were recruited. Mucosal candidiasis, Addison's disease and hypoparathyroidism were the most common clinical manifestations in these patients. One novel homozygous splice acceptor mutation (c.308-1G>C), and one novel heterozygous stop-gain mutation (c.1496delC) combined with a known heterozygous c.232T>C missense mutation were found. Moreover, we observed previously described splice donor (c.1095+2T>A), frameshift (c.967-979del), stop-gain (c.415C>T), and missense (c.62C>T) mutations among the patients. All results were co-segregated in parents. CONCLUSION: Here, we reported two novel mutations in the AIRE gene leading to APECED. Our data could provide insight into the phenotypic and genotypic spectrum of APECED in the non-Jewish Iranian population. These findings, in addition to future functional assays, can elucidate disease-causing mechanisms related to the AIRE gene and assist in genetic counseling and diagnosis.

Early and delayed puberty among Iranian children with obesity.

BACKGROUND: It has been hypothesized that puberty onset is disturbed as the children gain more weight. This study aimed to investigate the prevalence and risk factors of the puberty disturbances among children with obesity in Tehran, Iran. METHODS: This study was performed as a cross-sectional study, investigating 168 children with obesity from Tehran, Iran, from March 2018 to February 2019. BMI percentile more than 95% was considered as the inclusion criteria. RESULTS: Seventy-eight (46.4%) of the assessed children were females. The mean weight, height, BMI were 89.65 (±11.01) kg, 169.88 (±8.32) centimeters and 31.13(±3.8) kg/m2, respectively. There was no difference between males and females regarding the early puberty (P=0.098), but delayed puberty was significantly higher among males (P=0.029). Our results indicated higher birth weight is associated with earlier onset of obesity in children (P=0.044). CONCLUSIONS: Our study demonstrated no association between obesity and early puberty in girls; however, boys with obesity had delayed puberty. We also found higher birth weight is associated with earlier onset of obesity, putting light on the importance of preventive interventions.

Investigating Genetic Mutations in a Large Cohort of Iranian Patients with Congenital Hyperinsulinism

Objective: Congenital hyperinsulinism (CHI) is the most frequent cause of severe and persistent hypoglycaemia from birth. Understanding the pathophysiology and genetic defects behind hyperinsulinism and its complications provides clues to timely diagnosis and management. The aim of this study was to evaluate the underlying genetic aetiology of a specific Iranian pediatric cohort with CHI. Methods: A total of 44 unrelated children, 20 girls and 24 boys, with an initial diagnosis or history of CHI from all regions of Iran were recruited between 2016 and 2019. Targeted next generation sequencing (tNGS) was performed for the genes found in about half of CHI patients. Results: Mutations were identified in 24 cases (55%). Patients with a confirmed genetic cause were mainly diagnosed below age of one year old (p=0.01), had fewer other syndromic features, excluding seizure, (p=0.03), were less diazoxide responsive (p=0.04) and were more diazoxide unresponsive leading to pancreatectomy (p=0.007) compared to those with no identified mutations. Among 24 patients with identified genetic mutations, 17 (71%) had a mutation in ABCC8, 3 (12%) in KCNJ11, 3 (12%) in HADH, and 1 patient had a mutation in KMT2D. These included five novel mutations in ABCC8, KCNJ11, and KMT2D. Conclusion: This is the biggest genetic study of CHI in Iran. A high frequency of recessive forms of CHI, especially HADH mutations, in our study could be due to a high rate of consanguineous marriage. We recommend tNGS to screen for all the CHI genes.

p.Gln318X and p.Val281Leu as the Major Variants of CYP21A2 Gene in Children with Idiopathic Premature Pubarche.

Premature pubarche (PP) is the appearance of sexual hair in children before puberty. The PP phenotype may attribute to nonclassic congenital adrenal hyperplasia (NC-CAH). In this study, we investigated the role of CYP21A2 gene variants in patients with PP in the Iranian population. Forty patients (13 males and 27 females), clinically diagnosed with PP, were analyzed for molecular testing of CYP21A2 gene variants. Direct sequencing was performed for the samples. Also, gene dosage analysis was performed for the cases. Fourteen patients (35%) had a mutation of p.Gln318X and p.Val281Leu, out of which 10% had regulatory variants. Approximately 10% of the patients were homozygous (NC-CAH). 78.5% (11/14) of patients had trimodular RCCX of which 5 patients had two copies of CYP21A1P pseudogene. The prevalence of p.Val281Leu was higher than p.Gln318X in PP patients. In conclusion, CYP21A2 variant detection has implications in the genetic diagnosis of PP phenotype. The genetic characterization of the CYP21A2 gene is important for characterizing the variable phenotype of carriers and genetic counseling of PP and NC-CAH patients.

Role of vitamin D and vitamin D receptor gene polymorphisms on residual beta cell function in children with type 1 diabetes mellitus.

BACKGROUND: After the onset of type 1 diabetes mellitus (T1DM), preservation of the residual ß-cell function can help good metabolic control. The aim of this study was to evaluate the effect of vitamin D and its receptor gene polymorphisms on residual ß-cells function. METHODS: One hundred and one children with T1DM (new cases) older than 5 years were selected. Vitamin D receptor (VDR) gene polymorphisms, vitamin D (VD), fasting and stimulated C-peptide (FCP and SCP) levels were measured within 1.5 and 4.5 month after the diagnosis of disease. Kruskal-Wallis and Mann-whitney U test were used for comparing the study groups. Generalized estimating equation (GEE) model was used for the estimation of association between VD and VDR gene polymorphisms with FCP and SCP after adjustment for comorbid variables. RESULTS: The most frequent genotypes and alleles in TaqI, FokI, BsmI and ApaI polymorphisms were TT (50%) and allele T (68.88%), FF (59.2%) and allele F (77.04%), Bb (41.8%) and allele b (61.73%), and Aa (53.1%) and allele A (63.29%) respectively. In children with higher VD levels, the C-peptide (CP) levels were elevated. Also we observed: the tt genotype associated with increasing SCP levels compared with TT genotype; the bb and Bb genotypes were associated with increasing both FCP and SCP in comparison to BB; and the aa and Aa genotypes were associated with decreasing FCP in comparison to the AA genotype. CONCLUSIONS: Sufficient levels of VD (more than 30 ng/ml) can preserve residual ß-cells and insulin secretion.

Translation, cross-cultural adaptation, reliability and validity of the Persian version of the ACL-QOL questionnaire in patients with anterior cruciate ligament reconstruction.

BACKGROUND: Quality of life (QOL) measures can be used to make sound clinical decisions after reconstruction of the anterior cruciate ligament (ACL). The purpose of the present study was to translate and cross-culturally adapt the Anterior Cruciate Ligament Quality of Life (ACL-QOL) questionnaire into the Persian language and to evaluate its psychometric properties. METHODS: The process of translation and cross-cultural adaptation followed the World Health Organization method. One hundred and forty-five patients with ACL reconstruction (ACL-R) filled out the Persian versions of ACL-QOL and the SF-36 Questionnaire. The measurement properties of internal consistency, agreement, criterion validity, floor and ceiling effects were measured. 40 out of 145 patients with ACL-R completed the Persian version of the ACL-QOL questionnaire twice for the test-retest reliability. RESULTS: The questionnaire had high internal consistency (Cronbach's α = 0.96). The intraclass correlation was excellent for reliability and agreement in five domains and overall score (ICC 0.87, 0.74, 0.90, 0.85, 0.81 and 0.89; p < 0.001). The standard error of measurement and the minimum detectable change were found to be 3.28 points and 9.9 points, respectively. There was a strong correlation between each item and the total score of the Persian version of ACL-QOL questionnaire. The questionnaire showed strong and moderate criterion validity (r = 0.61, r = 0.37) with SF-36 physical component score and mental component score, respectively. No ceiling and floor effects were observed. CONCLUSIONS: Persian version of the ACL-QOL questionnaire has acceptable reliability and validity and can be used in assessing Iranians quality of life after ACL reconstruction.

A Genotype-First Approach for Clinical and Genetic Evaluation of Wolcott-Rallison Syndrome in a Large Cohort of Iranian Children With Neonatal Diabetes.

OBJECTIVE: Wolcott-Rallison syndrome (WRS) is an extremely rare autosomal recessive condition, characterized by permanent neonatal diabetes mellitus (PNDM) associated with skeletal dysplasia, growth retardation and liver dysfunction. WRS is caused by biallelic mutations in the gene encoding eukaryotic translation initiation factor 2alpha kinase 3 (EIF2AK3). METHODS: As part of a comprehensive study on clinical and genetic investigation of neonatal diabetes in an Iranian population, 60 unrelated Iranian subjects referred with PNDM were analyzed. All the probands were screened for KCNJ11, INS, ABCC8 and EIF2AK3 using a polymerase chain reaction-based sequencing approach. RESULTS: We identified 9 different variants in EIF2AK3 in 11 unrelated Iranian probands, of which 5 variants were shown to be novel and not reported previously. The diagnosis of WRS was made by molecular genetic testing and confirmed by clinical re-evaluation of the subjects. Clinical follow up of the affected individuals shows that in at least some of them, PNDM was associated with short stature, failure to thrive, neurodevelopmental delay, epilepsy and hepatic and renal dysfunction. There was a strong family history of neonatal diabetes in the families of the probands with a high mortality rate. CONCLUSION: WRS is a common cause of PNDM in children of consanguineous parents. Furthermore, clinical diagnosis of WRS would have been delayed or possibly missed without genetic testing because this study shows that the associated features of WRS might be obscured by a diagnosis of PNDM. Therefore EIF2AK3 should be considered for any infant and young child with PNDM, particularly if the parents are related.

The Effect of Metformin as an Adjunct Therapy in Adolescents with Type 1 Diabetes.

INTRODUCTION: The strict control of blood glucose levels in adolescents with Type 1 Diabetes Mellitus (T1DM) is accompanied with a considerable long term decrease in microvasular and macrovascular complications. AIM: This study was conducted to investigate the effect of metformin as an adjunct therapy in adolescents with poorly controlled Type 1 diabetes. MATERIALS AND METHODS: It was a quasi-experimental (an uncontrolled before and after) study. The study population consisted of the patients aged over 10 years with T1DM. Metformin tablet was added to patient's insulin therapy for 12 months. Haemoglobin A1c protein was measured in the beginning of the study and repeated with three months intervals till the end of it. Insulin dosage, Body Mass Index (BMI), serum lipid, creatinine and lactate level were measured twice; in the beginning of the study and at the end of it (after 12 months). Data was analysed by SPSS (version 18) software. Paired- t-test, Wilcoxon signed ranks test and Repeated Measure ANOVA were used to examine the study's hypothesis. A p-value <0.05 was considered as significant. RESULTS: Twenty nine patients were included in the study. HbA1c level and insulin dosage was significantly reduced (p<0.001) after one month of metformin as an adjunct therapy. Serum lipid was decreased (p=0.7). Weight (p<0.001) and BMI (p=0.007) were increased. CONCLUSION: Adjunctive metformin therapy reduced HbA1c value and the insulin dosage received in adolescents with T1DM.

Comparison of Bone Mineral Density in Common Variable Immunodeficiency and X-Linked Agammaglobulinaemia Patients.

BACKGROUND: Primary antibody deficiency (PAD) is the most common group of primary immunodeficiency disorders, resulting from different defects in the development and function of B cell lineage. Common variable immunodeficiency (CVID) and X-linked agammaglobulinemia (XLA) are two of the major types of PADs. Optimal growth and subsequently bone health could potentially compromise due to the interference of several factors in PAD with childhood onset. In the present study, our aim was to evaluate bone mineral density (BMD) of patients with CVID and XLA. METHODS: BMD of 37 CVID and 19 XLA patients was examined. Total BMD was determined by dual-energy X-ray absorptiometry and the calculated scores were compared internally and externally with age-sex matched and ethnic-specific reference. Related factors associated with bone density including immune-related complications, serum calcium, phosphate, total alkaline phosphatase, 25(OH) vitamin D and parathyroid hormone levels were recorded. RESULTS: The median age at the time of study was 20 years among all patients and was not statistically different between CVID and XLA groups and the mean of body mass index (BMI) was 19.4±4.6 kg/cm². Thirty-eight (67.9%) of total patients had normal BMD and 18 (32.1%) patients had a low BMD. BMI was positively correlated with BMD at lumbar spine and femoral neck. The number of low BMD patients in CVID (40.5%) group was more than the XLA (15.8%). CONCLUSION: Beside nutritional, gastrointestinal and infectious complications which are shared in both groups of patients, CVID patients are more prone to alteration of BMD due to association with lymphoproliferative and endocrine diseases. Therefore routine evaluation of bone density and treatment adjustment should be considered in all PAD patients particularly in CVID patients.

PTPN22 Single-Nucleotide Polymorphisms in Iranian Patients with Type 1 Diabetes Mellitus.

BACKGROUND: PTPN22 plays a crucial role in regulating the function of various cells of the immune system, particularly T cells. Polymorphisms of the PTPN22 gene have been associated with many autoimmune diseases, including type 1 diabetes (T1D) which is a T-cell-mediated disease. OBJECTIVE: The present study was aimed at genotyping of an Iranian population for five polymorphisms of the PTPN22 gene. METHODS: The study population consisted of 99 T1D patients and 100 healthy controls. We genotyped five single-nucleotide polymorphisms (SNPs) (rs12760457, rs1310182, rs1217414, rs33996649, and rs2476601) of the PTPN22 gene. RESULTS: Regarding the variant rs2476601, genotypes AG and GG were increased and decreased in T1D patients compared with controls, respectively. Further, alleles G and A of this SNP were found to be decreased and increased in T1D patients, respectively (p value = 0.001). However, T1D and control groups did not differ on genotype distribution or allele frequency for other investigated SNPs. CONCLUSIONS: The PTPN22 rs2476601 minor allele (A) was associated with T1D in Iran, accounting for its pathophysiology in autoimmune diseases.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy: report of three cases from Iran.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), also named as autoimmune polyglandular syndrome (APS) type 1, is a rare autosomal recessive disorder caused by mutations in autoimmune regulator (AIRE) gene. It is distinguished by an immune-mediated damage of endocrine tissues, chronic candidiasis, and ectodermal disorder. APECED has been shown to be frequent in some populations including Iranian Jews. Here we report three cases of APECED from two independent Iranian Muslim families. Addison's disease, hypoparathyroidismand mucocutaneous candidiasis were shared clinical manifestations in all patients. Mutational analyses have demonstrated a novel homozygous splice site mutation (c.1095+2T>A) in intron 9 and a previously identified homozygous nonsense mutation (c.415C>T) in exon 3 of patients respectively. Future studies are needed to evaluate the frequency of these variants in Iranian APECED patients which would facilitate genetic counseling as well as prenatal diagnosis.

Assessment of Vitamin D Status and Response to Vitamin D3 in Obese and Non-Obese Iranian Children.

BACKGROUND: Obesity seems to be a critical issue nowadays because of its high prevalence and its adverse effects on health. There is some evidence indicating the relationship between obesity and lower serum 25-hydroxyvitamin D [25(OH)D] concentration. The aim of the present study was to examine serum 25(OH)D status of obese and non-obese Iranian children and compare their therapeutic response with identical oral vitamin D3 treatment. METHODS: In a non-randomized clinical trial, serum 25(OH)D level of 45 obese and 45 non-obese Iranian children aged 2-14 years was measured. Those with serum 25(OH)D status <30 ng/ml (73 cases) were treated with one pearl of vitamin D3 (50 000 International Units) once a week for 6 weeks. Serum vitamin D was measured once more 2 weeks after treatment. RESULTS: The frequency of hypovitaminosis D was 43/45 (95.6%) in obese and 30/45 (66.7%) in non-obese children at baseline (p < 0.001). After treatment of 73 cases (43 obese, 30 non-obese), the above percentages were decreased to 24/43 (55.8%) and 1/30 (3.3%), respectively (p < 0.001). CONCLUSION: Our study demonstrated a high frequency of vitamin D deficiency among Iranian children, particularly the obese ones. Moreover, low therapeutic response in the obese group is witnessed.

Assessment of Sexual Maturation Among Girls With Special Needs in Tehran, Iran.

BACKGROUND: There is limited data on sexual maturation among girls with intellectual, sensory, or physical disabilities. OBJECTIVES: The present cross-sectional study was conducted to assess the sexual maturation of girls with these disabilities in special schools. METHODS: In this cross-sectional study, we evaluated the onset and progression of sexual maturation in 642 six to 18-year-old girls with intellectual, sensory, or physical disabilities from special schools in Tehran. The participants were selected by multi-stage random sampling. Pubertal stages were assessed by visual inspection and palpation based on the rating scales of Tanner. Stage two (breast budding and pubic hair growth) and stage five were considered the onset and end of puberty, respectively. RESULTS: The mean ages of onset of puberty indicated by breast budding (B2 stage) and by pubic hair growth (P2 stage) were 10.8 ± 1.48 and 10.79 ± 1.64 years, respectively. The process of puberty based on breast budding and pubic hair growth was completed at 15.58 ± 1.85 and 15.59 ± 1.8 years, respectively. The average height at the onset of puberty (stage B2) among participants was 128 ± 28.79 cm and the average weight was 8.31 ± 36.47 kg. CONCLUSIONS: Among our patients, the mean ages of onset of puberty indicated by breast budding (B2 stage) and by pubic hair growth (P2 stage) were 10.8 ± 1.48 and 10.79 ± 1.64 years, respectively. Compared to the data from healthy Iranian girls, our findings indicate that the mean age of pubertal onset among schoolgirls with disabilities is slightly higher than that of their healthy counterparts.

Hyperostosis-hyperphosphatemia syndrome (HHS): report of two cases with a recurrent mutation and review of the literature.

Hyperostosis-hyperphosphatemia syndrome (HHS) is a rare autosomal recessive metabolic disorder caused by mutations in the GALNT3 and FGF23 genes. The main features of this disorder include painful swelling of long bones, increased renal reabsorption of phosphate but normal renal function and vitamin D and parathormone levels. Previously, we reported a novel missense mutation in the FGF23 gene in a patient suffering from HHS. In the present report, we demonstrated the same mutation (c.471C>A) in two other cases of HHS with similar clinical manifestations. As this nucleotide change has not been reported previously, it can be a population specific mutation in Iran that can facilitate carrier testing and prenatal diagnosis of HHS.