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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]

Objective: Four combinations of five neutral sequence changes at rs713040, rs10768683, rs7480526, rs7946748, and rs1609812 occurring in the human beta globin gene defined as frameworks have been reported in beta globin gene. Here we report for the frequency of these frameworks in thalassemia major patients of North Iran. Methods: Beta globin gene frameworks of 46 thalassemia major patients of North Iran were determined using Denaturing Gradient Gel Electrophoresis. Findings: All these frameworks called framework 1, 2, 3, 3a were present at the frequency of 23.9%, 45.7%, 6.5% and 23.9% respectively. Conclusion: These frameworks may be used for tracking mutant alleles in prenatal diagnosis programs. [ABSTRACT FROM AUTHOR]

Objective: Prenatal diagnosis of β-thalassemia carrier couples has helped to prevent bearing affected children. Among 177 couples referred to our laboratory for prenatal diagnosis, 14 mothers had twin pregnancies. Methods: By using direct and indirect methods, we determined their mutations and linkage analysis using polymorphic markers (restriction fragment length polymorphism [RFLP]). Results: It was shown that in five families both fetuses were heterozygote carriers. In another five families, one fetus was normal and the other one was carrier. In two families, one fetus was affected and the other one was heterozygous carrier; in one case one fetus was affected and the other one was homozygote normal. In the last family both fetuses were homozygote normal. If all fetuses were fraternal then one would expect to see seven homozygote normal and the same number affected, and 14 carriers. Conclusion: Our results indicated that at least in cases where both fetuses had identical genotypes, then they may be identical twins. Molecular testing indeed showed that in three cases the twins were identical. Another point is that in three cases, one of the twin fetuses was affected and the other one was either normal or heterozygote in which only the affected fetuses were aborted by the specialist. [ABSTRACT FROM AUTHOR]