Long Term Use of Hydroxyurea In Patients with β-Thalassemia In Southern Iran

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2061-2061
Author(s):  
Mehran Karimi ◽  
Sezaneh Haghpanah ◽  
Majid Yavarian ◽  
Ali Farhadi ◽  
Abdolreza Afrasiabi ◽  
...  
Keyword(s):  
Side Effects ◽  
Blood Transfusion ◽  
Adverse Effects ◽  
Globin Gene ◽  
Gene Mutations ◽  
Beta Globin ◽  
Beta Globin Gene ◽  
Clinical Responses ◽  
Group 2 ◽  
Xmni Polymorphism

Abstract Abstract 2061 Introduction: Hydroxyurea(HU) is an antimetabolite agent that also promotes production of fetal hemoglobin (HbF). Reports on the use of HU in patients with thalassemia major (TM) have revealed a reduction in blood transfusion dependency. Due to lesser α/β globin imbalance in thalassemia intermedia (TI) compared with TM, better clinical responses are expected in patients with TI. This study was undertaken to evaluate hematological and clinical responses of patients with β-thalassemia to HU therapy as well as adverse effects of HU and Beta globin gene mutations of patients in a period of thirteen years in southern Iran. Methods: Two hundred patients; mean age of 21±7, ranged from 5 to 40 years enrolled in this study. Patients divided into two groups. Group 1 consisted of 143 transfusion-dependent thalassemia patients after age of two. Group 2 consisted of 57 TI patients without any history of blood transfusion or long interval transfusion. Mean dose of HU was 9.9±2 mg/kg/day, range of 8–15mg/kg/day. Response to HU was defined as increasing Hb level at least 1g/dl after 3 months of starting HU and/or decrease or cessation of the need for blood transfusion. Investigated variables included Hb, MCV, MCH, HbF, and HbA1 in laboratory results as well as spleen size, energy state, facial changes (head circumference), and the need for blood transfusion in clinical findings. The patients were followed by Hb electrophoresis, Complete Blood Count, serum ferritin and chemistry panel in appropriate intervals. The assessment of adverse effects in patients was conducted by pediatric hematologists. Genomic DNA extracted from peripheral leukocyte by Giagen DNA extraction kit. Beta globin gene mutations were determined by ARMS based PCR and confirmed by sequencing. XmnI polymorphism at -153 gG after PCR, was characterized by RFLP method and electrophoresis on 2% agarose. Statistical analysis was done by SPSS v. 15 using student’ t-test, paired t-test, and chi square test. Results: Of the 143 patients in group 1who were transfusion-dependent, 101 patients became transfusion-free and 28of them needed 1–4 transfusions per year. In this group, 14 patients had no response to HU and excluded from the study. All of the patients in group 2 were completely transfusion-free with acceptable Hb level at the end of study. Overall the mean Hb level of the patients after HU therapy was (9.4± 1.3). Exercise tolerance increased in 97% of the patients. No significant facial changes were observed in the patients at the end of study. From 73 non splenectomized patients, 83% had no change in spleen size. Adverse effects of HU were recorded in 44 of 200 patients. The most common side effects were dermatologic adverse effects followed by neurological and gastrointestinal side effects. Hematological malignancy and toxicity or any sign of bone marrow suppression were not observed in the patients during HU therapy. The presence of adverse effects in patients significantly increased by increasing age (p<0.001) and splenectomy (p< 0.05). But it had no significant relationship with sex, HU dose, or duration of treatment (p>0.05). Up to now, the frequency of beta globin gene mutations and XmnI polymorphism in 150 patients has been characterized (Tables 1 and Table 2). The most frequent beta globin gene mutation and XmnI polymorphism in our patients were homo IVS II-1(40.6%) and +/+ (59%) respectively. Conclusion: In our study HU was effective for decreasing or cessation the need of regular blood transfusion as well as increasing Hb level in β-thalassemia patients. Also all of the patients could tolerate low-dose treatment with HU in this period without any major side effects. So HU could be a safe alternative to blood transfusion in transfusion-dependent β-thalassemia patients after age of 2 or help to increase Hb level in untransfused TI patients. Disclosures: No relevant conflicts of interest to declare.

Major Beta-Globin Gene Mutations in Eastern India and Their Associated Haplotypes

1999 ◽  
Vol 49 (4) ◽  
pp. 232-235 ◽  
Author(s):  
Aditi Bandyopadhyay ◽  
Sanmay Bandyopadhyay ◽  
Manju Dutta Chowdhury ◽  
Uma B. Dasgupta
Keyword(s):  
Globin Gene ◽  
Gene Mutations ◽  
Beta Globin ◽  
Eastern India ◽  
Beta Globin Gene

Investigation of beta globin gene mutations in Syrian refugee patients with thalassemia major

2019 ◽  
Vol 44 (2) ◽  
pp. 126-129
Author(s):  
Hatice Çevirici ◽  
Can Acıpayam ◽  
Ebru Dündar Yenilmez ◽  
Fatma Burcu Belen ◽  
Esra Pekpak ◽  
...  
Keyword(s):  
Sequence Analysis ◽  
Globin Gene ◽  
Gene Mutations ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Amplification Refractory Mutation System ◽  
Beta Globin ◽  
Beta Globin Gene ◽  
Beta Thalassemia Major ◽  
Mutation System

Abstract Objectives This study, detection of beta globin gene mutations in thalassemia major patients who migrated from Syria to Kahramanmaraş region were planned. Materials and methods The study included 35 Syrian national beta thalassemia major patients. Beta globin gene mutations were detected by ARMS (Amplification Refractory Mutation System) method, RFLP (Restriction Fragment Length Polymorphism) method and DNA sequence analysis. Codon 15, codon 9/10, codon 5 and codon 8 mutations, which we could not detect with other methods in our study, were detected by sequence analysis. Results In beta thalassemia major patients, 16 types of mutations were detected, the most common being IVS-I-110 (n=8). Other mutations are according to frequency order IVS-II-745 (n=3), codon 44 (n=3), codon 15 (n=3), IVS-I-110/IVS-I-1 (n=3), codon 5 (n=2), IVS-I-1 (n=2), codon 8/IVS-II-1 (n=2), codon 44/codon 15 (n=2), IVS-II-1 (n=1), codon 39 (n=1), IVS-I-6/codon 5 (n=1), codon 9/10 (n=1), IVS-I-110/codon 39 (n=1), IVS-I-5/IVS-II-1 (n=1), codon 39/IVS-II-745 (n=1). Conclusions According to the results of our study beta-thalassemia mutations in Syrian immigrant groups show heterogeneity and mutation types of mutation map is similar to Turkey. The conclusion is to prevent families to have a second patient child by genetic counseling.

scholarly journals Beta-globin gene mutations in children with beta-thalassemia major from Sanliurfa province, Turkey

2011 ◽  
Vol 2011 (4) ◽  
pp. 264-268 ◽  
Author(s):  
Ali Aycicek ◽  
Ahmet Koc ◽  
Zeynep Canan Ozdemir ◽  
Hasan Bilinc ◽  
Abdurrahim Kocyigit ◽  
...  
Keyword(s):  
Globin Gene ◽  
Gene Mutations ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Beta Globin ◽  
Beta Globin Gene ◽  
Beta Thalassemia Major

scholarly journals Phenotypes of Hb Okayama Mutation

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4898-4898
Author(s):  
Rudra Ray ◽  
Ankita Biswas ◽  
Sunistha Bhattacharjee ◽  
Maitreyee Bhattacharyya
Keyword(s):  
Blood Transfusion ◽  
Gene Mutation ◽  
Globin Gene ◽  
Silent Mutation ◽  
Pcr Analysis ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Heterozygous State ◽  
Beta Globin ◽  
Beta Globin Gene

Abstract Introduction: Since its first detection in the year of 1983 very little has been reported about Hb Okayama mutation. Hb Okayama, reported as a silent mutation (Globin Gene Server Hb Var ID: 220, dbSNP rs713040), happened to be detected in the process of HPLC analysis for the measurement of HbA1c in Japanese diabetic patient [1,2,3]. Till date only few Hb Okayama has been reported from Japanese and Austrian ethnicity [2,3,4]. Its phenotypes and co-inheritance with other beta globin gene mutation is not yet known. In this study we report phenotypes of Hb Okayama in heterozygous as well as compound heterozygous state when it is co-existing with a common beta globin gene mutation. To the best of our knowledge no such study has been reported in world literature. Methodology: Two groups of patients- beta carriers requiring blood transfusion; and patients with low MCV, MCH but normal in HPLC were further investigated by molecular analysis. ARMS PCR analysis for beta globin gene mutation detection, GAP PCR for alpha deletion and triplication analysis and DNA sequencing (ABI 3500 Genetic Analyzer) to identify rare beta mutations were carried out. Result: Among around 300 patients subjected to molecular investigation over last three years there were 118 cases of thalassaemia trait (by HPLC and confirmed to carry a heterozygous common beta mutations by ARMS PCR analysis), but were requiring blood transfusion or behaving like intermedia. They were subjected to alpha globin gene triplication analysis by GAP PCR. There were 84 cases found to carry absence of alpha triplication with heterozygous beta mutation. Beta globin gene sequencing analysis of these 84 patients revealed that there were 4 patients carrying Okayama heterozygous mutation [ Figure 1, Figure 2 ] along with a common heterozygous beta gene mutation ( IVS 1-5 G>C mutation). HPLC report of these patients carrying Hb Okayama along with IVS 1-5 mutations in compound heterozygous state showed increased HbA2 values like that of beta trait [Table 1 ]. Another group of patients with low MCV, MCH but Normal in HPLC were subjected to alpha deletion analysis after ruling out low Ferritin level. There were 72 patients showing absence of alpha deletion by GAP PCR analysis and carried low MCV, MCH value with Normal HPLC parameters were also subjected to beta globin gene sequencing which revealed the presence of Hb Okayama mutation among two patients in heterozygous state [Figure- 1, Figure 2], who had HbA2 values in normal or border line range with low MCV, MCH levels [Table-2]. Discussion: HbA2 measurement is used as the marker for screening of beta trait. Silent beta-thalassaemia carriers represent normal HbA2 level which makes their identification difficult. Okayama mutation or Hb Okayama is known to be a silent mutation [1-4] with normal HPLC. Hb Okayama is structural beta variant with a change of amino acid ( His > Gln) at Codon 2 (CD 2). Change in the nucleotide sequence at 70603 position from T to A or C (CAT>CAA or CAG) of beta globin gene (NG_000007.3) causes this mutation. The phenotypic associations of Hb Okayama in thalassaemia have very little been known till date. There has been report of very high expression of HbF(70%) value in HPLC resulting from compound heterozygous mutations one of which being silent (Cap+1) [ 5] ; where as there are also reports where the phenotypes of compound heterozygous including a silent mutation showing normal HPLC parameters [ 6 ]. However, in those studies no information about the clinical history and blood transfusion is described. In this study Hb Okayama heterozygous co-inheriting with IVS1-5(G>C) heterozygous mutation showed beta trait like HPLC parameters though all the patients carrying these compound heterozygous mutations required blood transfusion. The silent feature of Hb Okayama was evident in the case of the patients carrying only Hb Okayama mutation who showed absolutely normal HPLC parameters with low MCV, MCH and none of them requiring blood transfusion. Conclusion: Beta globin gene expression analysis to understand the association of Hb Okayama mutation in heterozygous and compound heterozygous states will enable to explain the mechanism of its phenotypes. How this mutation interferes with the expression of HbF or switching of delta globin gene is also to be understood as the HbF levels in HPLC was found to be like beta traits in this study. Disclosures No relevant conflicts of interest to declare.

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