Molecular characterization of β-thalassemia intermedia: a report from Iran

Arab, Aida; Karimipoor, Morteza; Rajabi, Ali M.; Hamid, Mohammad; Arjmandi, Sedeigheh; Zeinali, Sirous

doi:10.1007/s11033-010-0557-5

Cited by 12 publications

(5 citation statements)

References 17 publications

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“…However, in the present study the G γ-globin gene Xmn I polymorphism was not detected in any patient with the genotype β + /β + or the β + /β wt . The latter findings are consistent with earlier reports that the Xmn I SNP is the commonest ameliorating factor in cases with β° mutations but not β + [4, 37]. However, in our study the percentage of TI patients having the Xmn I SNP was low, in consistency with an earlier report from Brazil (9.7%) [38] but inconsistent to previous reports from Iraq (56.8%) [4], Iran (51.9%), [28] Pakistan (23%) [14] and China (26.5%) [39].…”

Section: Discussionsupporting

confidence: 93%

Molecular characterization of β-thalassemia intermedia in the West Bank, Palestine

Faraon

Daraghmah²,

Samarah

et al. 2019

BMC Hematol

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Background We aimed to investigate the molecular basis of β-Thalassemia intermedia (TI) in the West Bank region and its management practices. Methods This was a case series multi-center study and included 51 cases of TI. DNA sequencing was used to analyze β-globin gene mutations. Common α-globin gene mutations were screened by Gap-PCR (−α 3.7 , −α 4.2 , −- MED , ααα anti3.7 ) or DNA sequencing (α2-IVS II 5 nt del). Xmn I -158 C > T polymorphisms of Gγ-globin gene was determined by RFLP-PCR. Results Seven β-globin gene mutations were observed, namely IVS-I -6 C > T, IVS-I-110 G > A, IVS-II-1 G > A, IVS-I-1 G > A, Codon 37 Trp > Stop, beta − 101 and IVS-II-848 C > A. Ten genotypes were observed. Homozygosity for IVS-I-6 accounted for the majority of TI cases with a frequency of 74.5%. The second common β-globin gene genotype was homozygote IVS-I-110 G > A (5.8%) and homozygote IVS-II-1 G > A (5.8%). The remaining seven genotypes were each detected in about 2% of patients. α-Thalassemia mutations were seen in five patients (9.8%), and included (−α 3.7 , ααα anti3.7 and α2-IVSII-5 nt del). Xmn I polymorphism was observed in four patients (7.8%), three homozygotes and one heterozygote. Conclusions Homozygosity for the mild β-globin gene IVS-I-6 allele was the major contributing factor for the TI phenotype among the study subjects. The role of Xmn I SNP and α-thalassemia mutations in ameliorating the TI phenotype was observed in few patients for each factor. The beta − 101 C > T mutation was diagnosed in one patient in homozygote state for the first time in Palestine.

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Section: Discussionsupporting

confidence: 93%

Molecular characterization of β-thalassemia intermedia in the West Bank, Palestine

Faraon

Daraghmah²,

Samarah

et al. 2019

BMC Hematol

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“…Furthermore, the sequence of the three common mutations in this study agreed with that of Baghdad, Central Iraq [21], whereas previous studies from other parts of Kurdistan, Iraq revealed that IVS I-6 was the most frequent β-thal mutation, detected at around 33% [19,20], which probably explains their higher reported frequency of β + β + or β 0 β + genotypes. Moreover, our results are consistent with that seen in different studies from Iran [24,25,27], including Iranian Kurds [28]. In contrast, IVS-I-6 was the most frequent β-thal mutation in Turkey [29], Lebanon [11], Egypt [30], Cyprus [22], and Italy [31].…”

Section: Discussionsupporting

confidence: 92%

“…β 0 -Thal mutation, on the other hand, amounted to 56.1% of the β-TI family genotype, which highly suggests the coinheritance of ameliorating factors including α-thalassemia and/or coinheritance of a single nucleotide polymorphism (SNP) in the three major quantitative trait loci (QTLs) for the continuous synthesis of Hb F to modify the α : β chain imbalance and to reduce ineffective hemopoiesis [23]. This has been particularly emphasized in studies from Iran, where β 0 mutations are more frequent in β-TI patients and XmnI polymorphism was found to be a considerable ameliorating factor [24,25].…”

Section: Discussionmentioning

confidence: 99%

Beta-Thalassemia Intermedia: A Single Thalassemia Center Experience from Northeastern Iraq

Amin¹,

Jalal

Ali

et al. 2020

BioMed Research International

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Objective. To determine the molecular characterization and disease-associated complications of beta-thalassemia intermedia (β-TI) patients in Sulaymaniyah province, northeastern Iraq. Methods. A total of 159 β-TI patients from 114 families were enrolled. Detection of β-thalassemia mutations was done by reverse hybridization technique and direct gene sequencing. Also, the clinical and hematological data were collected through an electronic-based medical recording system using a designed comprehensive questionnaire. Results. Nineteen different β-globin gene mutations arranged in 37 various genotypes were determined. The most frequent were IVS-II-I (G>A) (47.2%), followed by IVS-I-6 (T>C) (23.3%) and IVS-I-110 (G>A) (5%). Among disease-related morbidities documented, bone disease amounted to 53% (facial deformity and osteoporosis), followed by endocrinopathies 17.6% (growth retardation and subclinical hypothyroidism), cholelithiasis 13.8%, pulmonary hypertension 11.3%, and abnormal liver function test 7.5%, whereas venous thrombosis, extramedullary hemopoiesis, and leg ulcer were less frequently observed. Age≥35 and female sex were risk factors for cholelithiasis, while age was an independent risk for hypothyroidism and female sex was associated with increased risk for osteoporosis. Mean serum ferritin of ≥1000 μg/L was associated with an increased risk of osteoporosis, whereas chelation therapy was protective for a multitude of other complications. Transfusion, on the other hand, increased the risk of osteoporosis, yet it was protective for cholelithiasis and hypothyroidism. Moreover, splenectomy was protective for cholelithiasis, although it was an independent risk for hypothyroidism. Finally, hydroxyurea was associated with an increased risk of osteoporosis, while it was protective for cholelithiasis. Discussion and Conclusion. β+-thalassemia mutation had contributed to 41.25 of families with a less severe β-thalassemia phenotype in the northeastern part of Iraq, justifying the need to investigate the contribution of genetic modifiers in ameliorating disease severity. In addition, the substantial number of β-TI patients developed disease-related morbidities, which necessitates the need for more appropriate clinical management with earlier intervention.

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“…In particular, 70.3, 45.8 and 15.0% of GR, MR, and NR patients, respectively, were IVS-II-1/IVS-II-1. This pattern is likely due to linkage of the IVS-II-1 mutation with the XmnI T allele in the Iranian population (33,34).…”

Section: Resultsmentioning

confidence: 94%

The XmnI andBCL11ASingle Nucleotide Polymorphisms May Help Predict Hydroxyurea Response in Iranian β-Thalassemia Patients

et al. 2012

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Hydroxyurea (HU), a drug which can reactivate fetal hemoglobin (Hb F) production, is frequently prescribed to β-thalassemia (β-thal) patients. However, transfusion requirements of only a subset of patients are reduced upon HU treatment. Because of its potential side-effects, targeted prescription of HU is imperative. To identify genetic markers that correlate with drug response, we have carried out a retrospective association study of single nucleotide polymorphisms (SNPs) in three Hb F quantitative trait loci (QTLs): the XmnI polymorphism, BCL11A, and the HBS1L-MYB intergenic region, with the response to HU in a cohort of 81 transfusion-dependent Iranian β-thal patients. An increase in blood transfusion intervals post-therapy was used to measure drug response. Our results suggest that presence of the XmnI T/T genotype or the BCL11A rs766432 C allele correlates strongly with response to HU (p <0.001). Accordingly, these markers may be used to accurately predict the HU response of Iranian β-thal patients.

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Molecular characterization of β-thalassemia intermedia: a report from Iran

Cited by 12 publications

References 17 publications

Molecular characterization of β-thalassemia intermedia in the West Bank, Palestine

Molecular characterization of β-thalassemia intermedia in the West Bank, Palestine

Beta-Thalassemia Intermedia: A Single Thalassemia Center Experience from Northeastern Iraq

The XmnI andBCL11ASingle Nucleotide Polymorphisms May Help Predict Hydroxyurea Response in Iranian β-Thalassemia Patients

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