Thalassemic mutations in Southern Iran

Approximately 180 mutations have been described in beta-thalassemia worldwide with specific spectrum in each ethnic population. This study determines the spectrum and the frequency of beta-thalassemia mutations in patients with beta-thalassemia trait and sickle cell-beta-thalassemia. Fifteen compound heterozygous sickle cell thalassemia [SCT] and 23 beta-thalassemia trait patients were studied using reverse dot blot, denaturing gradient gel electrophoresis and direct genomic sequencing. We detected distinct beta-thalassemia alleles in 15 compound heterozygous of SCT and 23 beta-thalassemia trait patients. The most common mutation was IVSII-1[G-A], found in 15 of the 38 thalassemia chromosomes. IVSII.1 [G-A] mutation is a single nucleotide change of G to A at intervening sequence 2 position 1 of beta-globin gene, detected in 11 out of 23 chromosomes in A/beta-thalassemic patients and in four out of 15 chromosomes of SCT patients. This mutation constituted about 39% of the mutations in both groups. The -25bp 3 IVSI, deletion of 25 base pairs from 3' end of intervening sequence 1 of beta-globin gene, was found to be the second prevalent mutation among all chromosomes. Defining thalassemia mutations are necessary to establish prenatal diagnosis programs leading to lower medical cost. Amongst 10 different types of mutation detected in beta- thalassemic patients from South of Iran, two mutations of IVSII-1[G-A] and -25bp 3 IVSI were the most predominant beta-thalassemic alleles

Beta-globin gene cluster haplotypes in Iranian patients with beta-thalassemia

Beta-globin gene cluster haplotypes are useful in diagnosis of particular molecular defects in Beta-thalassemia, prenatal diagnosis of Beta-thalassemia, and elucidating population affinities. Beta-globin gene cluster haplotypes were studied in 150 Beta-thalassemia minor and 52 healthy in-dividuals from the Fars province of Iran. DNA was extracted from leukocytes of whole blood by phe-nol-chloroform. Haplotype was determined by PCR-RFLP technique. There were 26 out of 150 with homozygous haplotypes. Haplotype I was found as the most prevalent haplotype among both patients and normal individuals. Out of 26 patients bearing homozy-gous haplotypes, 12 [46.2%] had typical haplotype I and 3 [11.5%] had atypical haplotype I. The prevalence of haplotype I in normal control subjects was around 43% [45 out of 104 Beta A chromo-somes]. The second prevalent haplotype was haplotypes V [15.4%] and III [15.4%] for homozygous patients and controls, respectively. The most frequent mutation in patients was IVS II.1 [G-->A] that was not linked to a single haplotype. IVS I.110 [G-->A] mutation was linked to haplotype I. Mutation in codon 30 [G -->A] was associated with haplotype V. Being Haplotype I the most prevalent haplotype in Beta-thal and BetaA chromosomes, implies that Beta-thalassemia mutations might have arisen in the chromosomal background common in the popula-tion, rather than due to selection pressure or gene flow [migration]. Patients with haplotype IX had the highest HbF levels compared to other haplotypes