Background: One of the most important phenotypic modifying factors for thalassemia is the presence of Xmn1 polymorphism. This retrospective study was performed to investigate the overall prevalence of Xmn1 polymorphism among Iranian β-thalassemia patients with homozygote IVSII-1MUTATION and to assess the relationship between Xmn1 polymorphism with patients’ hemoglobin levels and the response to hydroxyurea (Hu) therapy. Materials and Methods: The present cross sectional study included 112 β-thalassemia patients with homozygote IVSII-1 MUTATION. Laboratory investigations included complete blood count and routine hematological indices were measured by Sysmex K1000 (Japan) blood auto analyzer. To find the state of Xmn1 polymorphism, blood samples were collected from patients using EDTA containers for genomic DNA analysis. DNA extraction and amplification-refractory MUTATION to determine the Xmn-1 polymorphism were performed. Results: In total, 206 thalassemia patients including 112 patients diagnosed as thalassemia major and 94 patients diagnosed as thalassemia intermediate entered the study. The mean age at the start of transfusion was 5 ± 6. 4 years old, and all of the patients received hydroxyurea. Twenty eight patients (14%) did not show any Xmn 1 polymorphisms (-/-), and 178 patients (86%) showed polymorphism either in one loci (-/ +, 44 patients, 21. 3%) or both loci (+ / +, 134 patients, 65%). Patients with Xmn1 polymorphism showed significantly higher age at diagnosis (p=0. 002), higher age at start of transfusion (p=0. 001), higher hemoglobin levels after treatment with hydroxyurea (p=0. 005), and lower transfusion dependency (P=0. 044). Conclusion: The presence of Xmn1 polymorphism led to a delay in onset of blood transfusions, higher hemoglobin levels, better response to hydroxyurea treatment and milder phenotypic presentation among thalassemia patients with IVSII-1 MUTATION.

Background: b -thalassemia, a monogenic autosomal recessive disorder, is prevalent in Middle East, particularly in Iran. In Iran, near to 20 MUTATIONs in the b-globin gene are introduced as common MUTATIONs with varying incidence frequencies in each city. Therefore, detection and screening for couples at high risk can help to solve the problems of this disease. In this study, optimized genotyping of two common MUTATIONs in Isfahan Province, IVSII-I (G-A) and FSC-8/9 insG, was performed using the T-ARMS method.Methods: In this case-control study, 10 healthy individuals and 30 patients affected by β-thalassemia major with a mean 24.76+4.5 years were selected from Omid Hospital in Isfahan Province. After designing tetra primers for two prevalent MUTATIONs IVSII-I (G-A) and FSC-8/9 insG, samples were genotyped using tetra-primers ARMS PCR technique.Results: We have developed a sensitive single tube tetra-primers PCR assay to detect both IVSII-1 (G-A) and FS8-9 insG MUTATIONs. Moreover, we have distinguished homozygous and heterozygous forms of these MUTATIONs successfully. The frequency of IVSII-1 (G-A) MUTATION from 30 patients in Isfahan was 86.6% (33.3% heterozygote, and 53.3% mutant homozygote) and for FS8-9 insG MUTATION was 16.6% (13.3% heterozygote, and 3.3% mutant homozygote).Conclusion: Tetra-primers ARMS PCR could be a reliable, accurate and simple technique for genotyping SNP and different MUTATIONs. So far, no study was done on optimization methods for genotyping MUTATIONs in b-thalassemia by T-ARMS. Here, we successfully adjusted and enhanced this method for recognizing two common MUTATIONs (FSC-8/9 insG and IVSII-I (G-A)) of b-thalassemia in Isfahan population.

Inclusion-cell (I-cell) disease (mucolipidosis II) is a rare inherited metabolic disorder resulting from a defective phosphotransferase, characterized by coarse facial features, skeletal abnormalities and mental retardation. As clinical feature of this condition mimic that of Hurler disease MUTATION studies help in the diagnosis. We present a case of I-cell disease in a neonate with Nacetylglucosamine-1-phosphate transferase alpha and beta subunits (GNPTAB) gene MUTATION.

Background: b-thalassemia is a common autosomal recessive disorder resulting from over 200 different MUTATIONs of beta globin genes. The aim of the present study was to identify the distribution and frequency of the most common b-thalassemia MUTATIONs among the population of Isfahan Province in central Iran.Methods: The data presented here were derived from a total of 114 b-thalassemia chromosomes of 18 affected patients and 78 unrelated carriers identified in our screening program. Furthermore, 23 pregnant women were analyzed among couples with a PND request for b-thalassemia. Allele identification was carried out using routine Reverse Dot Blot, ARMS, and genomic sequencing.Results: The most common MUTATION, IVS-II-I, followed by FSC-36-37, IVS-I-5, FSC-8-9, IVS-I-110, IVS-I,3’-end; -25bp, IVS-II-745, FSC-8, Cd-39, FSC-22-24, IVS-I-1, Cd-44, IVSII-2,3 (+11/-2), IVS-I-6, and FSC-16, respectively. The present study not only provides a guide for distribution and frequency of both recurrent and uncommon MUTATIONs, but also for the first time, reports a rare b-thalassemia MUTATION, IVSII-2, 3 (+11/-2), in the Isfahan province of Iran.Conclusion: The information presented here could greatly facilitate screening for b-thalassemia and prenatal diagnosis in the province of Isfahan.

Aim: We aimed to explore the frequency of BRAFV600E MUTATION in Iranian patients with colorectal cancer (CRC) as well as its association with clinic pathological characteristic of patients.Background: CRC is the third leading cause of cancer related death. There is a growing body of data showing the association of BRAFV600E MUTATION with malignant transformation and clinical outcome of different tumors, including CRC. These findings suggest that BRAFV600E MUTATION can be used as diagnostic and/or prognostic biomarker for management of cancer patients.Patients and methods: A total of 85 patients with sporadic tumor were recruited. BRAFV600E MUTATION was investigated using sequencing of extracted DNAs from formalin-fixed paraffin-embedded (FFPE) tumor tissues. Electropherograms were analyzed using Laser-gene 6 software.Results: More than 95% of patients were in stage I and II and none of them were in stage IV. Patients were mostly below 55 years old and tumors were dominantly located in the distal colon. Of note, no BRAFV600E MUTATIONs were detected in our population.Conclusion: Our results showed no V600E MUTATION in the BRAF gene in stage I and II of CRC patients. Further studies in multi-center settings are warranted to examine the prognostic and/or predictive value of this marker in different stages of colorectal cancer patients.

Introduction: Neonatal diabetes mellitus (NDM) is a rare disorder characterized by impaired blood glucose regulation that manifests before six months of age. Unlike autoimmune diabetes, NDM is caused by genetic MUTATIONs. One of the rarest causes of NDM is pancreatic agenesis, which results from MUTATIONs affecting the pancreas transcription factor 1A (PTF1A) gene and its enhancer. The following case report presents a rare instance of this condition. Case Presentation: This report describes a 2-year-old male child born to consanguineous Iranian parents, diagnosed with NDM due to pancreatic agenesis caused by a rare MUTATION in the PTF1A enhancer. Hyperglycemia was detected from the first day of life, and ultrasonography confirmed the absence of pancreatic tissue. Molecular analysis revealed homozygosity for the g.23508437A > G variant within the enhancer region of the PTF1A gene. At two years of age, with pancreatic enzyme replacement and insulin therapy, the patient exhibits normal neurological development, and his physical growth is at the 38th percentile. Conclusions: Based on previous studies, the g.23508437A > G variant in the PTF1A gene enhancer region should be considered in cases of pancreatic agenesis. While whole-exome sequencing (WES) remains the gold standard for genetic diagnosis, it may fail to detect certain MUTATIONs. Therefore, targeted evaluation of PTF1A is essential when a genetic etiology is suspected.

Background: Approximately 180 MUTATIONs have been described in β-thalassemia worldwide with specific spectrum in each ethnic population. This study determines the spectrum and the frequency of β-thalassemia MUTATIONs in patients with β-thalassemia trait and sickle cell-β-thalassemia.Methods: Fifteen compound heterozygous sickle cell thalassemia (SCT) and 23 β-thalassemia trait patients were studied using reverse dot blot, denaturing gradient gel electrophoresis and direct genomic sequencing.Results: We detected distinct β-thalassemia alleles in 15 compound heterozygous of SCT and 23 β-thalassemia trait patients. The most common MUTATION was IVSII-1(G→A), found in 15 of the 38 thalassemia chromosomes. IVSII.1 (G→A) MUTATION is a single nucleotide change of G to A at intervening sequence 2 position 1 of β-globin gene, detected in 11 out of 23 chromosomes in A/β-thalassemic patients and in four out of 15 chromosomes of SCT patients. This MUTATION constituted about 39% of the MUTATIONs in both groups. The -25bp 3 IVSI, deletion of 25 base pairs from 3' end of intervening sequence 1 of β-globin gene, was found to be the second prevalent MUTATION among all chromosomes.Conclusion: Defining thalassemia MUTATIONs are necessary to establish prenatal diagnosis programs leading to lower medical cost. Amongst 10 different types of MUTATION detected in β- thalassemic patients from South of Iran, two MUTATIONs of IVSII-1(G→A) and -25bp 3' IVSI were the most predominant β-thalassemic alleles.