Pectrum of β-Globin Gene Mutations Among Thalassemia Patients in the West Bank Region of Palestine

Abstract

β-Thalassemia (thal) is an autosomal recessive disorder that results in hypochromic hemolyticanemia in affected patients. In the West Bank area of Palestine, the prevalence of β-thal trait isapproximately 3.5% among the population, with an estimated 120,000 carriers. Seventeen β-globingene mutations could be identified in 148 patients using polymerase chain reaction (PCR),amplification refractory mutation system (ARMS)-PCR and direct sequencing. The predominantmutations included: IVS-I-6 (T→C) (28.7%), IVS-I-110 (G→A) (17.6%), codon 37 (G→A)(10.4%), IVS-I-1 (G→A) (9%), codons 106/107 (+ G) (6.8%) and codon 39 (C→T) (4.6%). Otherless frequent and rare mutations included: IVS-II-1 (G→A), codon 5 (–CT), IVS-II-848 (C→A),–30 (T→A), codons 8/9 (+ G), IVS-I-5 (G→C), –28 (A→C), IVS-II-745 (C→G), codon 6 (–A),codon 27 (G→T) and codon 30 (AGG→ACG). Most patients (62.2%) were homozygous for one typeof mutation, while the rest (27.3%) were compound heterozygotes. Some patients were heterozygous forβ-thal and sickle cell anemia traits. No mutations could be detected in both alleles of eight patients,while in seven patients only one mutant allele could be detected. Further investigations are needed toresolve the corresponding genotypes of these patients. This study represents a comprehensive investigationof the type, frequency, and distribution of thalassemia mutations among the Palestinian population inthe West Bank region of Palestine. A degree of similarity and significant variations was evident in thetype and frequency of mutations when the present mutations profile was compared with similar onesamong various Arab and non Arab populations. The association between the identified mutations and thecorresponding genotypes of our patients with specific polymorphism frameworks in the β-globin gene wasperformed and the results revealed linkage disequilibrium.