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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]

Little is known about the social determinants of health (SDH) of taking the prenatal diagnosis (PND) test as a pivotal strategy to prevent occurrences of β-thalasssemia major (β-TM). This study sought to evaluate the relationship between socio-demographic characteristics of parents and taking the PND test at Zahedan, Iran from 2015 to 2016. The design of the present study was a case-control. Data on socio-demographic characteristics of parents including age, education, job, ethnicity, and family relationships, kind of marriage as well as pre marriage test status and PND test status, were obtained from registered medical records. The relationship between socio-demographic characteristics and taking the PND test was evaluated using binary logistic regression. The study included 256 β-thalassemia (β-thal) carrier couples who were referred to the Zahedan Prenatal Diagnosis Center to take the PND test and 47 β-thal carrier couples who already had a newborn with β-TM and had not taken the PND test. Univariate analysis showed that the higher education level of the father, consanguineous parents, official marriages, pre marriage test and consultation, significantly increased the odds of taking the PND test. The significant relationships were not observed in multivariable analysis, however, pre marriage tests and official marriages can be considered as determinants of taking the PND test with odds ratio (OR) [95% confidence interval (95% CI)] of 14.67 (0.64, 334.93) and 3.41 (0.55, 20.94), respectively. Our results provided evidence in which socio-demographic characteristics of the parents may determine their taking the PND test. [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 aim of this study was to evaluate the degree of acceptability of prenatal diagnosis and voluntary termination of pregnancy in case of a fetus affected with β-thalassemia major (β-TM) in patients and their parents in Southern Iran. We interviewed 510 parents who had β-TM children and 254 patients. A questionnaire was used to record information regarding sex, age, parents' and patients' knowledge about prenatal diagnosis, and their decision regarding abortion of an affected fetus. Of 764 participants, 565 (73.9%) knew a little about prenatal diagnosis and 198 (25.9%) had no knowledge at all, while 711 (93%) were in favor of prenatal diagnosis and 53 (6.9%) were not. Specifically, 663 subjects (86.7%) were in favor of early termination of pregnancy in case of an affected fetus, while (13.2%) were not. Compliance with prenatal diagnosis was high, and the main reason for declining was its cost. No particular correlations were found between the size of the household, the education or the economic level, and the request for early termination of pregnancy of an affected fetus. The decision not to have a medical abortion correlated with religious beliefs only. [ABSTRACT FROM AUTHOR]

β-Thalassemia (β-thal) is a major health problem in Iran and the incidence of carriers is around 3–4%. The disease is caused by heterogeneous mutations in the β-globin gene and is characterized by hypochromic microcytic anemia. The human β-globin complex spans a region of 70 kb and contains over 20 restriction fragment length polymorphisms (RFLPs). At least nine RFLP markers including RsaI/β in the β-globin gene cluster have been routinely exploited for prenatal diagnosis. Here, we report a novel polymorphism upstream of the β-globin gene characterized by RsaI digestion. Sequencing of a fragment containing this area showed a nucleotide change (T>C) at position −223 upstream of the β-globin gene. This change could interfere with precise interpretation of the RsaI digestion pattern in linkage analysis and prenatal diagnosis of β-thal. [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]