Genetic screening in Iranian patients with retinoblastoma.

PurposeThe most common intraocular tumor in childhood, retinoblastoma, is largely associated with mutations in the RB1 gene. In the most comprehensive RB1 screening in Iran, we evaluated the RB1 mutations in 106 patients with retinoblastoma, including 73 bilateral (heritable) and 33 unilateral (sporadic) cases.Patients and methodsMutations were identified using amplification refractory mutation system (ARMS) PCR and direct sequencing of the 27 coding exons of RB1 and multiplex ligation-dependent probe amplification (MLPA).Results and ConclusionWe found 33 (31%) and 64 (60%) patients with sporadic unilateral and bilateral retinoblastoma, respectively as well as 9 (8.5%) cases with hereditary bilateral retinoblastoma. In total, we identified 52 causative RB1 mutations in 106 patients (global mutation rate of 49%). Of the 52 patients, 48 (92%) had sporadic and familial bilateral and 4 (8%) had sporadic unilateral RB. Therefore, the detection rate of RB1 mutations was 66% (48/73) and 12% (4/33) in bilateral and unilateral cases, respectively. Mutations were classified as nonsense in 31 (60%), missense in 1 (2%), large deletion in 11 (21%), small deletion in the 7 novel (15%) and splice site mutation in 2 (4%) patients with RB. Of 31 nonsense mutations, 23 (74%) occurred in the 11 Arginine codons of the RB1. Seven mutations (13%) were novel, and 45 (87%) had been previously reported. Thirty-three mutations were single-base substitutions leading to 31 nonsense amino acid changes and 2 splice site mutations in introns 12 and 16 of RB1. The altered 3D model structures of the RB1 novel mutant proteins are also predicted in this study.

Long-term follow-up of ninety eight Iranian patients with primary immune deficiency in a single tertiary centre.

PURPOSE: The aim was to describe the clinical manifestations, complications and long-term outcome of a cohort of Iranian patients with primary immune deficiency (PID). METHOD: We retrospectively studied the demographic, clinical and immunological characteristics of the PID patients in a single tertiary centre, from January 1989 to July 2014. The patients were classified according to the International Union of Immunological Societies Expert Committee on PID. RESULTS: 98 patients were diagnosed with and followed-up for 15 disorders. The mean age at onset and diagnosis and the diagnostic delay were 8±10, 14.2±13.1 and 6.1±7 years, respectively. Parental consanguinity rate was 57%. Predominantly Antibody Deficiency was the most common diagnosis (n=63), followed by congenital defects of phagocytes (n=16), combined immunodeficiencies (n=12), well defined syndromes (n=4) and defects in innate immunity (n=3). Recurrent sinopulmonary infection was the most common presentation. Active infections were treated appropriately, in addition to prophylactic therapy with IVIG and antimicrobials. Not all the patients were compliant with prophylactic regimens due to cost and unavailability. One SCID patient underwent successful bone marrow transplantation. The total mortality rate was 19% during the follow-up period (7.8±7.6 years). The mean age of living patients at the time of study was 23±11.7 years. CONCLUSIONS: Physicians awareness of PID has been rising dramatically in Iran, ensuring an increasing number of patients being diagnosed and treated. More effective treatment services, including health insurance coverage and drug availability are needed to improve the outcome of PID patients.

A Comparison of Efficacy Between Recombinant Activated Factor VII (Aryoseven) and Novoseven in Patients With Hereditary FVIII Deficiency With Inhibitor.

INTRODUCTION: This study compared the efficacy of Aryoseven with Novoseven to control bleeding episodes in patients with hemophilia A with inhibitors. METHODS: Sixty-six patients were randomized into 2 groups, with 4 consecutive block randomization. These groups received Aryoseven and Novoseven dosages of 90 to 120 µg/kg intravenously every 2 hours. RESULTS: Median (interquartile range) level of factor VIII (FVIII) inhibitor in groups A and B was 15.0 and 19.0 Bethesda Unit (BU) preadministration. Bleeding onset in group A was 1246 ± 1104 minutes and in group B was 2301 ± 1693 minutes (P = .311). The Kavakli global response scores and treatment success rate was comparable in both the groups. The side effects in groups A (9.7%) and B (2.9%) were comparable. CONCLUSION: Biosimilar recombinant activated FVII is found to be as effective as Novoseven in the treatment of acute joint bleeding in patients with hemophilia with inhibitors. Its usage will decrease the gaps in hemophilia.

Expression analysis of microRNA-125 in patients with polycythemia vera and essential thrombocythemia and correlation with JAK2 allele burden and laboratory findings.

INTRODUCTION: The JAK2V617F mutation has emerged in recent years as a diagnostic as well as a treatment target in patients with polycythemia vera (PV) and essential thrombocythemia (ET). The disease phenotype is also influenced by other factors such as microRNA (miRNA) deregulation. The aim of this study was to investigate miR-125 expression level in these patients with those obtained from healthy control subjects and its correlation with JAK2 allele burden and laboratory findings. METHODS: In total, forty patients with a clinical diagnosis of PV and ET were examined at the time of diagnosis. Ten healthy subjects were checked as controls. We performed JAK2 V617F allele burdens measurement and expression analysis of miR-125b-5p, miR-125b-3p, miR-125a-5p, and miR-125a-3p in leukocytes isolated from peripheral blood by quantitative real-time polymerase chain reaction. RESULTS: MiR-125b-5p and miR-125a-5p were upregulated in both patients with PV (P = 0.00 and P = 0.003, respectively) and ET (P = 0.02 and P = 0.002, respectively). In PV group, a significant correlation was observed between miR-125a-5p and platelet counts (P = 0.01, r = 0.531). The correlation between miRNA and JAk2 allele burden was not significant. CONCLUSION: In conclusion, our data indicate that other factors such as aberrant miR-125 expression may influence on the disease phenotype in patients with PV and ET.

A comparison between recombinant activated factor VII (Aryoseven) and Novoseven in patients with congenital factor VII deficiency.

In order to establish the efficacy and biosimilar nature of AryoSeven to NovoSeven in the treatment of congenital factor VII (FVII) deficiency, patients received either agent at 30 µg/kg, intravenously per week for 4 weeks, in a randomized fashion. The primary aim was to compare FVII:coagulation activity (FVII:C), 20 minutes after recombinant activated FVII (rFVIIa) injection, in the 2 groups. A secondary measure was self-reported bleeding. The median interquartile baseline range of the plasma level of activated FVII (FVIIa) activity in the 2 groups was 1.6 (1.1-14.0) IU/dL and 5.0 (1.1-25.5) IU/dL. All patients achieved levels of FVIIa (FVII:C) >30 IU/dL, 20 minutes after the injection of rFVIIa. Bleeding was similar between the 2 groups, with a comparable decrease in severity and frequency compared to the last month prior to treatment. AryoSeven is similar to NovoSeven in increasing postinjection FVIIa activity as well as in clinical safety and efficacy.

Classification of Iranian patients with Glanzmann's Thrombasthenia using a flow cytometric method.

Glanzmann's Thrombasthenia (GT) is a rare inherited autosomal recessive platelet disorder caused by a deficiency or dysfunction of the GPIIb-IIIa receptor on platelets, which is characterized by a lack of platelet aggregation in response to multiple physiologic agonists and a life-long bleeding disorder. Flow cytometry is a rapid and highly sensitive method that can detect reduced levels of receptors, as well as absolute deficiency. The aim of this study was to classify Iranian GT patients by a flow cytometric method, and to correlate these findings with the severity of clinical bleeding. The expression of GPIIb-IIIa on the platelet surface was assessed in 123 GT patients using quantitative flow cytometry to determine the most common subtype among these patients. We used a panel of antibodies to detect the expression of glycoproteins GPIb, GPIIb, GPIIIa, as well as Integrin αv. Patients were also interviewed with regard to the severity and frequency of bleeding, according to history and gender, in order to evaluate the nature of their bleeding phenotype, and classify them as mild, moderate or severe bleeders, in accordance with the Glanzmann's Thrombasthenia Italian Team (GLATIT) protocol. In the detailed analysis of the results of our investigation, 95 out of 123 (77.5%) were classified as type I; 20 (16%) as type II with residual GPIIb-IIIa, and eight (6.5%) as GT variants. The variant type was diagnosed by the inability of GPIIb-IIIa to bind fibrinogen, as evidenced by the absence of platelet aggregation in response to physiologic agonists. There was no significant correlation between bleeding severity and different subtypes of GT. This study demonstrates that GT type I is the most common subtype among Iranian patients. There was no correlation between severity of symptoms and cytometric phenotype of the disease. The identification of families at risk may significantly decrease the incidence of the severe form of the disorder if genetic counseling is provided.

Endocrinopathies in patients with transfusion-dependent beta-thalassemia.

Thalassemia is common in Iran. Appropriate therapy for this disease includes a regular blood transfusion and chelation therapy. However, in this approach patients will inevitably experience side effects, particularly iron overloads in critical organs, including heart, ductless glands, and liver. This study attempted to determine prevalence of adenoidal abnormality between Iranian thalassemia patients for prediagnosis and to offer necessary medical measures. This is a descriptive nonrandomized study and included all the patients suffering from thalassemia major referring to medical centers linked with the Iranian blood transfusion organization from January 2004 to January 2005. All patients were sampled for CBC, FBS, 2-h BS, HbAlC, liver function, renal function, and endocrine disease. Initially, reports of adenoidal experiments as well as other associated parameters were provided from medical records. A total of 437 patients enrolled in the study: 5.4% suffered from diabetes, 1% had hypothyroid, and 1 person showed hypoparathyroidism. The mean levels of ferritin in diabetic and nondiabetic groups and hypothyroid and nonhypothyroid groups were not significantly different. The mean levels of ferritin among various age groups also were not significantly different. Results of a comparison between present research and similar studies conducted throughout Iran and those performed abroad on adenoidal abnormalities in thalassemia patients show that subject patients of this study statistically suffered from fewer difficulties than diabetes patients in other studies.