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

Abstract

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.

Genotype-phenotype correlation and mutation spectrum of HBB gene in the Hatay province of Turkey

“…Differently, the presence of a transfusion history among individuals with homozygous IVS-I-6 (T>C) genotype in our study was 61%, which was lower than the 81% reported in the Palestine study 16 . In a previous study on the homozygous IVS-I-1 (G>A) genotype, which we detected with the second frequency in our study, it was reported that the cases were transfusion dependent 15. However, in our study, whereas two of the three homozygous IVS-I-1 (G>A) genotypes had a history of regular transfusion, one case was followed up independently of transfusion.…”

“…Although the homozygous IVS-I-110 (G>A) genotype is typically more common in our region and country, this genotype was less frequent in our study 9,13 . Instead, IVS-I-6 (T>C) was the most common genotype, and this finding is similar to previous research in Palestine and Israel [14][15][16] .…”

Mutation in thalassemia syndrome and clinical manifestation

“…IVS II-1 (G>A) is a β˚ mutation and is common in Mediterranean regions (16). In agreement with previous studies on the mutation spectrum of the beta-globin gene in Iranian populations and thalassemia intermedia patients, IVS II-1 (G>A) was considered as the most frequent beta-globin mutation among the patients investigated in this study (1,2,4,6,(17)(18)(19)(20)(21)(22). This is contradicted by the finding in Kuwait (23), Iraq (24) and some other ethnic groups (25,26).…”

Determining the current prevalence of β-thalassemia variants in Jordan

“…This study demonstrated the diversity of b-thalassemia alleles in North Jordan and is in line with the outcomes of the current study, in which three variants were classified as common at different percentages [7]. The common frequent alleles in Jordan are generally similar to those found in other studies in Jordan [8,9]. If supported by future research, these findings can provide updated data on the spectrum of b-thalassemia variants in Jordan, making the study valuable and reference-worthy [10].…”