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β-Thalassemia (β-thal) is one of the most common diseases in Iran. Here, we report the spectrum of HBB gene mutations in 176 Kurdish β-thal carriers from the northern part of Ilam Province, Iran. The amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) technique was used to identify common β-globin gene mutations observed in Iran. Samples negative on ARMS-PCR were analyzed by direct sequencing of the β-globin gene. In total, 12 different mutations were identified on the β-globin gene. The mutations of IVS-II-1 (G>A) ( HBB : c.315+1G>A), codons 8/9 (+G) ( HBB : c.27_28insG), codons 36/37 (-T) ( HBB : c.112delT) and IVS-I-110 (G>A) ( HBB : c.93-21G>A), were the most prevalent mutations in our samples, with frequencies of 59.09, 10.80, 7.95 and 7.39%, respectively. In general, the mutation spectrum of the β-globin gene in the northern part of Ilam Province is most similar to that in other western provinces of Iran. On the other hand, due to the high prevalence of carriers and β-thal major (β-TM) patients in this province, our results can be helpful in identifying carriers as well as at-risk fetuses through the prenatal diagnosis program.

In order to identify the α-thalassemia (α-thal) mutation spectrum in Kurdistan Province, West Iran, a total of 217 individuals, including 154 α-thal carriers and 63 normal subjects were investigated in this study. Molecular analysis of α1- and α2-globin genes using multiplex gap-polymerase chain reaction (gap-PCR), amplification refractory mutation system (ARMS)-PCR or direct DNA sequencing, showed 11 different α-globin variants. The -α 3.7 (rightward) deletion (NG_000006.1: g.34164_37967del3804) (70.32%), polyadenylation signal (polyA2) site (AAT A AA>AAT G AA) (α polyA2 α) ( HBA2 : c.*92A>G) (7.74%), -α 4.2 (leftward) deletion (6.45%) and codon 59 (or Hb Adana) (G>A) (αα codon 59 ) ( HBA1 : c.179G>A) (4.52%) were the most frequent mutations in the present study. In conclusion, the spectrum of α-thal mutations in Kurdistan Province is closest to that in western provinces of Iran (Kurdish and Laki populations). In addition, it was revealed that the codon 59 mutation is common in the Kurdish population. On the other hand, despite the same ethnic background of Kurds in Iran and Iraq, the - - MED I double gene deletion and polyA2 point mutation have different distributions in these two populations. Therefore, further studies are needed to identify the cause of these differences.

We describe a novel compound heterozygous genotype which consists of two point mutations named Hb Adana ( HBA1 : c.179G>A) and codon 127 ( HBA2 : c.382A>T) in a Kurdish family with two girls affected with severe α-thalassemia (α-thal). Both patients (the proband and her sister) had a history of splenectomy during childhood. Although the proband had no blood transfusion history, her affected sister has had two blood transfusions so far. In conclusion, diagnosing and reporting new genotypes on the α-globin genes will improve our knowledge about complicated genotype-phenotype correlations in α-thal disorder.

α-Thalassemia (α-thal) is one of the most common genetic disorders worldwide. The aim of this study was to investigate for the first time the α-thal mutation spectrum in the Lak population living in Lorestan Province, Iran. One hundred and seventy-six α-thal carriers participated in the study. Multiplex gap-polymerase chain reaction (gap-PCR), amplification refractory mutation system (ARMS)-PCR and direct sequencing were used for the detection of different mutations on the α-globin ( HBA1 and HBA2 ) genes. A total of 11 different mutations was identified. The -α 3.7 (rightward; NG_000006.1: g.34164_37967del3804) deletion was observed most frequently (56.35%), followed by α -5 nt α ( HBA2 : c.95+2_95+6delTGAGG), α polyA2 α ( HBA2 : c.*92A>G) and - - MED I (NG_000006.1: g.24664_41064del16401), with frequencies of 15.47, 9.39, and 6.08%, respectively. These four mutations accounted for more than 87.0% of the total mutated alleles. Moreover, 19 different genotypes were identified. The types and distribution pattern of the mutations identified in this study, in comparison with other studies conducted in Iran, was most similar to the Kurdish population of Kermanshah Province, Iran. Due to the lack of information on α-thal in Lorestan Province, it was not possible to compare the mutation spectrum in the Lur and Lak populations. In conclusion, our results may help in setting up a strategy for an α-thal screening program and genetic counseling in the Lak people.

β-Thalassemia (β-thal) is the most frequently observed hereditary blood disorder that results from genetic defects causing deficient synthesis of hemoglobin (Hb) polypeptide chains. Detecting thalassemia mutations are necessary for prenatal diagnosis (PND) programs leading a better quality of life for the patients, as well as a reduction in the cost of their medical care. There are more than 900 different genomic mutations of the β-globin gene described in the human hemoglobin variant (HbVar) database. In this study, we identified a mid-intronic mutation at IVS-II-821 (A>C) ( HBB : c.316-30A>C) position in the HBB gene of an Iranian proband and two of her siblings that was associated with β-thal clinical features. Direct DNA sequence analysis was performed by mutation scanning of the β-globin gene. Based on the observed β-thal phenotype and bioinformatics analysis results, we concluded that this β-globin gene mutation was associated with a mild phenotype of β-thal through activating potential splice sites by creating exonic splicing enhancers (ESEs), exon-identity element (EIE) and exonic splicing regulatory sequences (ESRs) sites.

Thalassemia is the most common inherited disorder in Iran. There are approximately 800 different genomic alterations of the β-globin gene described in the HbVar database. In this study, we identified a novel mutation in a 21-year-old woman [IVS-II-648/649 (-T); HBB: c.316-202del)] and describe its clinical implications. Two other members of this family, all with hematological and clinical features associated with β-thalassemia (β-thal), also carried this mutation. The molecular diagnosis of the β-globin gene mutation was performed by direct sequencing. Based on the observed β-thal phenotype and in silico analysis results, we concluded that this novel β-globin gene mutation was associated with the mild phenotype of β-thal.