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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]

Background: Cystic fibrosis (CF) is a multiorganic autosomal recessive disorder, caused by mutation in cystic fibrosis transmembrane conductance regulator (CFTR). CF is highly heterogeneous in Iranian population and molecular diagnosis based on direct identification of mutations is not completely efficient. The use of polymorphic intragenic markers not only can facilitate phenotype prediction in prenatal diagnosis by gene tracking, but also can lead to the demonstration of possible associations between haplotypes and specific mutations. Methods: 60 CF patients and 53 fertile normal subjects originating from North of Iran were analyzed for F508del mutation and c.1210-12T(5_9), c.1408A>G and c.744-33GATT(6_8) polymorphisms. Results: c.1210-12T[7] is the most prevalent allele in normal individuals and CF non-F508del patients with 87.7%and 86.7% frequencies respectively. c.1408A>G survey showed that frequency of allele G and A is nearly equal in both non-F508del CF patients and normal individuals. c.744-33GATT(6_8) study showed that 7 repeat is the most prevalent allele in normal individuals and non-F508del CF patients with 80.2% and 82.1% frequencies respectively. The [c.1408A; c.1210-12T[9]; c.744-33GATT[6]] haplotype was only associated with mutant alleles including F508del. Conclusions: The allelic distribution and heterozygosity results suggest that c.1408A>G, c.1210-12T(5_9) and c.744-33GATT(6_8) can contribute to carrier detection and prenatal diagnosis of CF in Iranian families with previous history of the disease. [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]

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]

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]