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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. [ABSTRACT FROM AUTHOR]

β-Thalassemia (β-thal) is one of the most common hemoglobinopathies worldwide and is caused by mutations on the β-globin (HBB) gene. The aim of the present study was to determine the mutation spectrum of the β-globin gene in β-thal carriers who were originally from Hamadan Province, Western Iran. Two hundred and eighty-two β-thal carriers participated in the study. Amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and direct sequencing were used for detection of different mutations. A total of 25 different mutations, including 21 β-thal mutations and four other hemoglobin (Hb) variants, in 280 β-thal carriers (99.3%) were detected in the present study. Three types of mutations including IVS-II-1 (G>A) (HBB: c.315+1G>A) (26.24%), codons 8/9 (+G) (HBB: c.27_28insG) (14.54%) and codons 36/37 (–T) (HBB: c.112delT) (12.76%) accounted for more than 50.0% of the identified mutations. Moreover, IVS-I-110 (G>A) (HBB: c.93-21G>A), codon 44 (–C) (HBB: c.135delC) and IVS-I (25 bp deletion) (HBB: c.93-21_del), had frequencies of 7.09, 7.09 and 5.67%, respectively. Allele frequencies of the remaining 19 mutations were less than 5.0%. This study is the first comprehensive study on a large sample size in Hamadan Province, Iran. In conclusion, the present study significantly increased the spectrum of HBB gene mutations in Hamadan Province compared with previous studies. Therefore, these results can be helpful in identifying β-thal carriers and at-risk fetuses through prenatal diagnosis (PND). [ABSTRACT FROM AUTHOR]

Our study aimed to determine the number of couples with normal hemoglobin (Hb) electrophoresis and low-borderline hematological values, which may come up with a clinically critical status in their offspring. The number of couples at risk for severe α-thalassemia (α-thal) needed to be estimated before recommending genetic counseling and prenatal diagnosis (PND). During the past 14 years, from at least 7000 referrals, 754 couples were investigated for α-thal by direct mutation detection methods followed by reverse strip assay and α-globin gene sequencing for inconclusive cases. Detection of silent β-thalassemia (β-thal) mutations was done in suspected cases by complete β-globin gene sequencing. We were able to provide a molecular diagnosis in 87.3% (658/754) of couples. A total of 9.1% (60/658) may have a clinically significant hemoglobinopathy in their offspring. Significant conditions included hydrops fetalis (20.0%; 12/60), certain Hb H (β4) genotypes (78.3%; 47/60) and β-thal intermedia (β-TI) (1.7%; 1/60). The diagnostic flowchart for couples with microcytic hypochromic anemia in countries with a high prevalence of hemoglobinopathies should include α and β gene sequencing. As our results indicate, every nine out of 100 of these couples will face significant hemoglobinopathies and every two out of 100 can carry Hb Bart's (γ4) hydrops fetalis in their pregnancies. For such cases, PND should be utilized to allow the carrier couples to decide whether or not to abort the fetus. [ABSTRACT FROM AUTHOR]

The marginal zones of the Caspian Sea and the Persian Gulf have a higher prevalence of thalassemia compared to other regions of Iran. This disease has disabled many people and resulted in increasing health care costs. The aim of this study was to assess the incidence of β-thalassemia (β-thal) and to evaluate the outcome of applied preventive strategies over a 14-year period in Fars Province, Southern Iran. This cross-sectional study comprised all new cases of β-thal recorded during 1997-2011. The data were obtained from the Non-Communicable Diseases Surveillance Department of Shiraz University of Medical Sciences, Shiraz, Iran, and are presented as mean ± standard deviation (SD). The Fars Health Network System screened 840 686 males and females applying for marriage certificates. Among the carriers, 50.5% cancelled their marriages, 42.5% married, and 7.0% did not show up at the clinics. The rate of cancelled marriages has reduced since 2000, when marriage candidates were given the option of prenatal diagnosis. From 2000 to 2011, a total of 3539 married couples were referred for prenatal diagnosis. Of these, 806 fetuses were found to carry thalassemia and 800 aborted. It is impressive to note that while 101 cases of thalassemia were recorded in 1997, this figure was reduced to two cases by 2011. This study has established that an integrated primary health care approach, with good infrastructure for implementing successful strategies, can significantly reduce the incidence of β-thal. [ABSTRACT FROM AUTHOR]

Hb Constant Spring (Hb CS, codon 142, TAA>CAA, α2) (HBA2:c.427T>C) and α2 IVS-I donor site (GAGGTGAGG>GAGG - - - - -) (HBA2:c.95++2_95++6delTGAGG) are nondeletional α-thalassemia (α-thal) mutations found all over the world. Identification of α-thal genotypes in at-risk couples for severe anemia or in highly heterogeneous populations requires rapid, accurate and cost-effective genotyping methods. In this study, a pair of primers were used to specifically amplify an 883 bp fragment from the α2-globin gene in order to simultaneously identify these two mutations by a PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) method. We determined the genotypic frequencies of Hb CS and the α2 IVS-I donor site mutations after amplification and enzymatic digestion with Tru9I in 238 northern Iranian samples referred for α-thal testing. Hb CS and the α2 IVS-I donor site mutations accounted for 21 (8.8%%) and 29 (12.2%%) of the nondeletional cases. This genotyping assay has proven to be a rapid, reliable and useful diagnostic tool for simultaneous detection of these two anomalies for genetic counseling or further prenatal diagnosis. [ABSTRACT FROM AUTHOR]

We report the spectrum of ββ-thalassemia (ββ-thal) mutations observed in a cohort of at-risk couples, who presented for prenatal diagnosis at the Thalassemia, Hemophilia and Prenatal Diagnosis Genetic Research Center, Shiraz Medical University, Fars, Iran, from March 2001 to April 2002. Using polymerase chain reaction-amplification refractory mutation system (PCR-ARMS), restriction fragment length polymorphism (RFLP) and direct sequencing technologies, in different combinations, we were able to provide preventive medical abortions to 55 couples at-risk of having an affected fetus. Fetal samples of chorionic villus (63.6%%) or amniocentesis (37.6%%) were collected according to the gestational age. The average presentation age was 11.6 ±± 2.6 weeks. The expected prevalent mutations were IVS-II-1 (G>A, 23.6%%) and IVS-I-110 (G>A, 10.0%%) followed by IVS-I-5 (G>C, 6.4%%) and IVS-I, 25 bp deletion (8.2%%). [ABSTRACT FROM AUTHOR]

β-Thalassemias are a group of heterogenous recessive disorders common in many parts of the world. Despite the great advances in the treatment of thalassemia, there is so far no cure, but perhaps bone marrow transplantation (BMT) is a possibility. Prevention, using prenatal diagnosis and selective abortion in the cases where the fetus is found to be affected, should be considered as a sensible alternative. During the past 5 years, 112 couples have been referred to our Center for detection of their β-thalassemia (β-thal) carrier status. In this group, common and rare mutations were detected. Of these, 106 couples (94.6%) came for counseling during pregancy and six (5.4%) came before becoming pregnant. Prenatal diagnosis was performed for the 106 couples at risk. Fetal DNA was obtained from both chorionic villus sampling (CVS) (99) and amniotic fluid (7). Using reverse hybridization, 64 (60.4%) were found to be heterozygous for a β-thal mutation and 24 (22.6%) were normal. Eighteen (17.0%) were found to carry an affected fetus and these pregnancies were terminated. [ABSTRACT FROM AUTHOR]