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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.

This study aimed to characterize the molecular spectrum of β-thalassemia (β-thal) mutations and evaluate the services available for prenatal diagnosis (PND) among the Sistani population of Iran. Mutations were analyzed with amplification refractory mutation system (ARMS), gap-polymerase chain reaction (gap-PCR), multiplex ligation-dependent probe amplification (MLPA) analysis and direct sequencing. Fetal diagnosis was also confirmed by linkage analysis. Over a 9-year period (2002-2011), 405 at-risk Sistani couples were referred for mutation analysis and/or PND. Of the referred couples, 18.5% had one to three affected children with β-thal major (β-TM) and the remainder had no children or were not married. Most of the couples (73.3%) lived in urban areas and the rate of consanguineous marriage was 76.8%. Twenty-one mutations were identified, of which the most frequent ones were IVS-I-5 (G>C) with a frequency of 74.1%, followed by codon 15 G>A (5.0%), codon -88 (C>T) (3.8%), IVS-II-1 (G>A) (3.4%), codons 8/9 (+G) (2.9%) and IVS-I-1 (G>T) (2.7%), which accounted for about 91.9% of the total β-thal mutations for this region. Furthermore, fetal DNA was obtained from chorionic villus sampling (CVS) for 266 pregnant women and 68 (25.5%) fetuses were diagnosed as affected. In summary, β-thal mutations are very heterogeneous and significantly different from those found in other parts of Iran and are similar to those of Pakistani and Indian populations. These results could greatly facilitate timely and accurate PND.

Objective: Despite premarital screening, prenatal diagnosis and the option for voluntary termination of pregnancy, some Iranian couples continue a pregnancy with a fetus affected with beta-thalassaemia major (β-TM). We examined the reasons for this decision, to evaluate the sociocultural challenges these couples face., Methods: A retrospective evaluation of medical records of all fetuses aborted was conducted to identify those with β-TM, to determine the frequency of β-TM births and to establish the number of couples with β-thalassaemia who declined prenatal diagnosis or a termination of pregnancy in this period. We investigated the reasons for declining these options., Results: The birth prevalence of β-TM decreased from 39.38 to 2.68 in 100,000 live births from 2005 to 2010. Terminations of pregnancy for affected fetuses increased from 67 in 2005 to 135 in 2010. We identified eight couples as β-thalassaemia carriers who declined prenatal diagnosis or a termination of pregnancy. All but one couple already had a child with β-TM. The reasons for declining prenatal diagnosis were strong religious beliefs, superstition and faith in a supernatural solution in six couples. Economic and cultural factors, and previous termination of pregnancy were also mentioned as reasons by the other two couples., Conclusion: Although most of the couples had a β-TM child and related socioeconomic problems, their reasons for refusing prenatal diagnosis or termination remain a challenge for the healthcare system in Iran. Couple screening and educational programmes have effectively decreased the rates of refusal in at-risk couples in recent years.

This study was performed to determine the molecular spectrum of β-thalassemia (β-thal) mutations in at-risk couples from Khorasan-e-Jonobi Province in East Iran. During the past 9 years, 106 couples were referred to our Center for detection of their β-thal carrier status. Samples were initially tested for the most common Iranian α- and β-thal mutations by gap-polymerase chain reaction (gap-PCR) and amplification refractory mutation system (ARMS)-PCR, respectively. In cases with negative results, direct DNA sequencing was used to identify additional β-globin mutations. Fetal DNA was obtained from chorionic villus sampling (CVS) (n = 55), 47.2% were referred during pregnancy and 23.0% of couples underwent more than one prenatal diagnosis (PND). Of the 14 mutations that were detected in Khorasan-e-Jonobi Province, Iran, the IVS-I-5 (G>C) and codon 44 (-C) mutations were the most frequently identified variants, representing 45.9 and 24.8% of the total; these were followed by three mutations in the following order: -88 (C >T) (5.3%); codons 8/9 (+G), a rare mutation, and codons 37/38/39 [-7 nucleotides (nts)], each with a frequency of 4.5%. These findings provide complementary information on the region specific profile of β-thal in eastern Iran.

Objective: To determine the molecular spectrum of β-thalassemia mutations among at-risk Balouch couples in Iran., Methods: Mutations' detection in DNAs extracted from the blood of partners of at-risk couples was characterized, and chorion villus sampling by amplification refractory mutation system and DNA sequencing was performed. Fetal diagnosis was also confirmed by linkage analysis., Results: Out of a total of 1234 at-risk Balouch couples referred to the center for prenatal diagnosis (PND) from June 2002 to June 2010, a high percentage of '67.4%' were from consanguineous marriages and 37.4% had between one and four affected children. The trend in referring gradually increased from 34 cases in 2002 to 357 cases in 2010. The astonishing finding was that, unlike most previous studies, only IVS 1-5 with an unusual frequency of 87.20% along with codon 8/9 (+G) with 4% constitutes about 91% of mutations. Altogether, 729 PNDs were made in 583 couples, 25% of whom had over one PND, and surprisingly five PNDs were made in the same woman within just 8 years., Conclusion: Regarding the limited types of frequent mutations among Balouch population, it is hopefully believed that the incidence of β-thalassemia could be controlled by a correct diagnosis in the due time., (Copyright © 2011 John Wiley & Sons, Ltd.)

Background and Aims: Thalassemias are the commonest monogenic diseases worldwide. Mutations in genes coding for the globin proteins that alter protein output, produce the thalassemia syndromes. This study aimed to present the cases of alpha-thalassemia in beta-thalassemic patients from Khuzestan province in Iran., Materials and Methods: A total of 227 subjects (10-45 years, mean age of 14·8 years) including thalassemia patients (n=43), and their parents and siblings (n=184) from unrelated Khuzestani families were included in this study. The standard diagnostic marker for beta-thalassemia is elevation of the hemoglobin A2 (HbA2) level (>3·5%), while low mean corpuscular volume (MCV<80) and mean cell hemoglobin (MCH<27) with a normal HbA2 level indicate alpha-thalassemia carrier., Results: The amplification refractory mutation system polymerase chain reaction confirmed that among 227 subjects, 147 (64·75%) were heterozygous beta-thalassemia patients and 80 (35·25%) were identified either normal or with unknown mutations. Out of these 147 patients, nine cases were diagnosed as compound heterozygous. The IVS11-1(G-C) mutation was found in majority of chromosomes (40·08%). Out of nine beta/alpha-thalassemia patients, four showed -α(3·7)/αα (1·76%), two had -α(3·7)/-α(3·7) (0·88%), one had -α(4·2)/αα (0·44%) and one had - -MED/αα (0·44%) genotypes., Conclusion: The present study suggests the need to establish a program for genetic counseling and prenatal diagnosis of beta-thalassemia for affected families and for initiating a control program by prospective screening of pregnant women. The application of the knowledge about mutation pattern was found to be beneficial since the mutations could be screened in the order in which they are present in our population. Hence, it will not only help to reduce the screening cost but also to promote early genetic counseling and prevention of an affected child.

The aim of this study was to investigate the prevalence and spectrum of beta-thalassemia (beta-thal) mutations in the population of Sunni Muslim Kurds in western Iran and to set up a prenatal diagnostic laboratory. Sixty unrelated Kurdish beta-thal patients identified in hematology clinics from different cities were studied. The mutations in 120 chromosomes were studied by polymerase chain reaction-amplification refractory mutation system and direct sequencing methods. We found fifteen beta-thal mutations, and IVS-II-1 (G>A) was the most frequent, comprising 35% of all mutations. Other common mutations were frameshift codons 8/9 (+G) 15.7%, IVS-I-1 (G>A) 8%, FSC 5 (-CT) 6.7%, FSC 8 (-AA) 6.7%, and IVS-I-110 (G>A) 6%. This is the first comprehensive study in this region and could provide a reference for prenatal testing and genetic counseling in this population.

We recently found a rare beta(0)-thalassemia (beta(0)-thal) mutation, namely codons 37/38/39 (-GACCCAG), in a consanguineous family from southeast Iran. The first cousin couple was heterozygous for the mutation. They had a healthy 4-year-old daughter and were referred to us for prenatal diagnosis at 6 weeks gestation in the second pregnancy. The fetus, based on results of sequencing of the beta-globing gene, was homozygous for the same mutation. Results of amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) on detection of this 7 bp deletion, and also restriction fragment length polymorphism (RFLP) analysis confirmed the homozygosity of the fetus.

In the present study, we report the first case of a 619 bp deletion on the beta-globin gene, found in a family from Kerman Province, Iran. This mutation is frequent in Pakistan, but it has not been previously reported in any part of Iran. This study revealed that all family members have this beta(0)-thalassemia (beta(0)-thal) mutation.

Background: Genetic disorders due to kindred marriages are common medical conditions in Iran; however, the legal aspects of abortion remain controversial. This study was undertaken to determine physicians' opinions regarding the termination of pregnancy for three genetic diseases: thalassemia major, hemophilia, and Down's syndrome., Methods: A questionnaire was administered to selected physicians by stratified random sampling to determine the following: age, gender, knowledge about prenatal diagnosis of diseases in high risk pregnancies, agreement with abortion, recommended gestational age for abortion, and, if opposed to abortion, the reason., Results: Of 323 physicians, who participated in the study, 91.3(295), 40.6(131), and 78.6%(254) were in agreement and 8.7(28), 59.4(192), and 21.4%(69) were opposed to abortion for thalassemia major, hemophilia, and Down's syndrome, respectively. Among 289 physicians opposed to abortion in respect of each of all three conditions, the following reasons were cited: religion, 18; emotional, 10; quality of care, 23; hope to find a new treatment option in the future, 103; miscellaneous reasons, 6; and a combination of these reasons, 129. Among 680 physicians in agreement with abortion in relation to all of the diseases, 4.6%(31) were agreed with abortion in less than 12 weeks gestation, 79.2%(538) in less than 16 weeks gestation, 5.6%(38) in less than 20 weeks gestation, 2.2%(15) in less than 24 weeks gestation, and 8.4%(58) were agreed with beyond the 24 weeks of gestational age., Conclusion: The majority of physicians were in agreement with abortion for thalassemia major and Down's syndrome because of the overall prognosis, but opposed to abortion for hemophilia.

Prevention programs are considered to be a top priority in Iran because beta-thalassemia (beta-thal) major (TM) is the most common autosomal disorder in Iran, and in the Mazandaran Province in particular. The main strategies comprise providing appropriate information for the public and professionals, screening and counseling of families at-risk and screening of general population prior to marriage. Providing laboratories for prenatal diagnosis was the most recent step in the program. We report the results of our prevention campaign for the period 1993-2006 in order to assess the effectiveness of all actions in controlling thalassemia major. In 1993, 500 TM patients were registered at the clinic of the Boo Ali Sina Hospital, Sari, Mazandaran, Iran. From 1993 to 1996, on average of 50 new cases were added to the cohort annually, whereas from 1995 to 2005 the number of new cases declined to 35 per year. Furthermore, the patients' average age increased. Overall, 51% of couples at-risk, who received genetic counseling, decided not to marry. All at-risk couples who are married were counseled for prevention of unplanned pregnancies. Currently, 64% are using safe contraceptive methods of family planning, and 14% are no longer at-risk for further pregnancies, the rest remained at-risk for unplanned pregnancies. In conclusion, at the relatively low cost of premarital screening and genetic counseling, we have offered at-risk couples the possibility of preventing the birth of at least 600 undesired TM patients. Thus, a great deal of suffering and an unbearable financial burden has been prevented to patients and their families.

For 14 years, Iranian scientists have worked to develop a national thalassemia prevention program. Although historically abortion was considered unacceptable in Iran, intensive consultations led to the clerical approval of induced abortion in cases with beta-thalassemia major in 1997, and a nationwide prevention program with screening, counseling and prenatal diagnosis (PND) networks has been developed. This paper reports the experience from one of the two national PND reference laboratories. As one of the oldest reference laboratories, we performed a total of 906 PND in 360 couples at risk for thalassemia from 1990 to 2003. Direct and indirect mutation detection methods were applied for all cases. In total, 22 mutations were tested routinely, and an additional 30 rare mutations were identified. 208 fetuses were found to be normal, 215 fetuses had beta-thalassemia major, and 435 fetuses were carriers of the trait. In 40 cases, we only defined one allele. In 8 cases, we were unable to provide any diagnosis, corresponding to 0.9%. Our data support the functionality of the Iranian beta-thalassemia prevention program. The success of this system in Iran, a multiethnic and Islamic-based country, would mean that it might be applied as an adaptive system for neighboring and other Islamic countries.

The beta-thalassemia (thal) minor phenotypes with normal Hb A2 levels and decreased MCV and MCH values are relatively rare beta-thal traits. Here, we describe a family with normal Hb A2 and decreased MCV and MCH levels. Amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) revealed the IVS-II-1 (G-->A) mutation in the beta-globin gene of the proband and her father. Direct sequencing of the gamma-globin gene of the proband and her father also revealed a previously reported variant called Hb A2-Troodos [gamma116(G18)Arg-->Cys] [in cis with the IVS-II-1 (G-->A) beta0-thal mutation]. This is the first case report of Hb A2-Troodos in association with the beta0 IVS-II-1 mutation. Reduced Hb A2 expression by a concomitant Hb A2 beta-thal in cis or trans, may cause problems in carrier diagnostics, and eventually in genetic counseling and prenatal diagnosis when insufficient molecular analyses are performed.

Thalassemias are the most common hereditary diseases in Iran, resulting from synthesis defects in one or more hemoglobin (Hb) subunits. The majority of patients suffer from beta-thalassemia (thal), but cases with microcytic hypochromic anemia and normal electrophoretic patterns are suspected to have alpha- or silent beta-thal. A family from the northern part of Iran, an area highly prevalent for thalassemias, was referred to us for prenatal diagnosis. The hematological data of the father indicated a pattern of beta-thal minor. Reverse hybridization analysis for the most common beta-globin mutations identified IVS-II-1 (G-->A) in the heterozygous state. The maternal laboratory data indicated a case more compatible with alpha-thal. Iron deficient anemia was ruled out, and common alpha-thal point mutations and deletions were investigated. As no mutation was detected, chain synthesis was performed and showed an alpha/beta chain ratio of 2.1, that was in the range of beta-thal minor. DNA sequencing of the entire beta-globin gene identified a heterozygous GTG-->GGG (Val-->Gly) mutation at codon 126, also known as Hb Dhonburi (Neapolis). Prenatal diagnosis of the fetal DNA showed the absence of the IVS-II-1 and codon 126 anomalies. This result demonstrates the importance of screening of individuals with mild microcytic hypochromic anemia for both alpha- and silent beta-thal mutations.

We report two new substitutions, IVS-I-108 (T-->C) and -27 (A-->T), identified in a couple at risk for beta-thalassemia. One is of Iranian origin and presents with two mutations: a new substitution of T-->C at nucleotide IVS-I-108, which is a silent polymorphism, and a previously described beta-thalassemia mutation at nucleotide -28 (A-->C). The other is from the island of Corsica, the only place in France where beta-thalassemia is endemic. He presents a new substitution of A-->T at nucleotide -27 in the TATA box, which was also found in several members of his family with the beta-thalassemia trait. The fetus was found to have inherited both these novel mutations.

Background and Objectives Thalassemia is the most common monogenic disease worldwide inherited in autosomal recessive manner. Beta-thalassemia is caused by mutations in beta-globin gene. It is characterized by reduction in red blood cell indices including low MCV, low MCH, high RBC count, low HbA1 and high HbA2. Considering these symptoms, finding a relation between erythrocyte indices and kind of mutations can be used as a rapid method in mutation diagnosis and initial screening of carriers. Materials and Methods In this descriptive-analytical study after DNA extraction from 200 beta- thalassemia minors in Khuzestan province by salting out method, we amplified and sequenced beta-globin gene by Sanger sequencing. Finally, we analyzed statistically the beta-globin gene mutations and erythrocyte indices association by SPSS. Results Our results showed that IVSII-1(G > A) is the most common mutation with 22.5% frequency in this population of beta-thalassemia carriers. We found that MCV index variations have a meaningful association with beta-globin gene mutations and the highest mean of MCV (65.4 ± 3.7) was observed in IVSI-110(G > A) mutation. Conclusions The results comply with many other studies performed in this field and can be used for rapid detection of mutation in carrier parents and prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Background & Objectives: Beta-thalassemia is one of the complex diseases that causes many social and economic problems for the patient and his family. This study aimed to investigate factors influencing the birth of thalassemia (intermedia or major) in family members with thalassemia major in Sistan and Baluchistan province. Materials & Methods: This descriptive-analytical study was conducted by census sampling on 48 families of thalassemia major patients with at least two children with thalassemia (intermedia or major) in their members. Data were collected through direct interviews and a review of patients' documents. The results were analyzed by SPSS (version 22) and Mann-Whitney U, Independent t-test, Wilcoxon, and Chi-square tests. Results: In this study, statistical evaluations showed that the birth of thalassemia in family members with thalassemia major whose mothers are housewives was 100% and in families that had no premarital counseling was 91.7%. There was a significant relationship between variables related to mothers' awareness of thalassemia, including their place of residence and Sistani and Baluchestani ethnics, and the birth of thalassemia in family members with thalassemia major (in both cases, P-value = 0.05); However, there was no significant relationship between other variables related to mothers' awareness such as age groups and maternal education with the birth of thalassemia in family members with thalassemia major (P-Value = 0.98 and P-Value = 0.22, respectively). Conclusion: Informing and educating before marriage for high-risk families with thalassemia children, as well as financial support for low-income families can inform parents, prevent the birth of thalassemia, and improve the quality of life of these patients. [ABSTRACT FROM AUTHOR]

Background: Beta-thalassemia is common in the Mediterranean area as well as the Middle East and India. Official report in Iran revealed the average prevalence rate of carriers about 4%. More than 20 restriction fragment length polymorphisms (RFLPs) are known in the beta-globin gene cluster and used in the prenatal diagnosis (PND) services. Some of these locations may have low allele frequency and are not informative in the prenatal diagnosis. The current study aims to find new haplotypes and polymorphisms with high allele frequency in the local population. Methods: Two thousand three hundred fifty samples (1,321 male and 1,029 female) from the northern Iran, whom suspected to be the carriers either for alpha or beta thalassemia and referred to the local diagnostic laboratory as a routine services were investigated during five years, (2010-2015). The beta-globin gene was sequenced for all samples. Results: Heterozygosity for five SNPs in the beta-globin gene was calculated separately. 383 individuals (16.29%) showed no sign of nucleotide change in the beta-globin gene sequence. In total, codon2 (C/T) 31.72%, IVSII-16 (C/G) 31.72%, IVSII- 74 (G/T) 54.71%, IVSII-81 (C/T) 19.47%, and IVSII-666 (T/C) 31.72% were seen respectively. Although all five polymorphisms showed reasonably high heterozygosity, IVSII-74 (G/T) [GG wild type (36.5%), G/T (54.71%) and TT (8.8%)] revealed the highest heterozygosity rate. Four combinations of these five SNPs were defined as new haplotypes named M1 to M4. ARMS-PCR also were designed and applied to detect IVSII-74 (G/T) nucleotide position. Conclusions: This study represents an intragenic polymorphism, IVSII-74, a reliable position with high heterozygosity rates in Iranian population for PND analysis. Trial registration: Retrospectively registered. [ABSTRACT FROM AUTHOR]

Objective To evaluate the repercussions of recent changes to the cut-offs used in the first screening step of the pre-marital screening programme for thalassaemia prevention in Iran. Methods The profiles of 984 subjects referred to a genetic laboratory, and the tests of 242 parents of children with thalassaemia major were assessed for red blood cell (RBC) indices, haemoglobin (Hb) A2 levels and results of Hb electrophoresis. Results Of 407 suspected thalassaemia minor (STM) cases, 18 proved positive for thalassaemia minor on molecular analysis (18/407, confidence interval 2.6–6.9%). If the revised screening cut-offs had been used to determine who would undergo molecular analysis, two of these cases would not have been identified. Only 4.4% of suspected cases with lower than normal RBC indices (mean corpuscular volume <80 fl and mean corpuscular Hb <27 pg) and HbA2 (<3.5%) were diagnosed with thalassaemia minor. Conclusion The thalassaemia major prevention programme is performed in two separate steps. One step involves the screening of subjects and identification of β-thalassaemia minor, suspected cases for thalassaemia minor (STM), and normal subject groups. The other step concerns the identification of thalassaemia minor in the STM group. Changing the cut-offs at the first screening step does not result in significant improvement from an economic view, and is associated with significant risk at the second screening step. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to evaluate the effectiveness of prenatal diagnosis (PND) for the prevention of thalassemia in Southern Iran.Methods: From 2004 to 2012 1346 couples with β-thalassemia minor were referred to our center. Mutation analyses utilized different methods including polymerase chain reaction-based technique of amplification refractory mutation system (ARMS), Restriction Fragment Length Polymorphism Analysis of PCR-Amplified Fragments (PCR-RFLP) and Gel Electrophoresis and direct sequencing. Haplotype analysis of the β-globin gene cluster was done routinely using the PCR-RFLP technique.Results: Of the 1346 couples, 884 (66%) requested PND. They had a total of 985 pregnancies (954 singleton and 31 twin pregnancies): the 1016 fetuses underwent chorionic villus sampling (CVS). Thalassemia major was diagnosed in 266 cases (26.2%), and termination of pregnancy was requested by the parents in 264 of them (99%). Thalassemia trait was detected in 499 (49.1%) and 251 cases (24.7%) showed no β-thalassemia mutations. There were three misdiagnoses (0.4%) (affected children diagnosed as carriers at PND). A unique pattern of thalassemia mutations was present in the study population, with IVS II-I (G→A), C36-37(-T), IVS I-5(G>C), -25bpdel (252-276), IVS I-110(G>A) and C44 (-C) being present in 62% of cases.Conclusion: The pattern of distribution of thalassemia mutations differs among ethnic groups within the same country. [ABSTRACT FROM AUTHOR]

Background: Thalassemic disorders are the most prevalent monogenic hereditary diseases around the world caused by decreased and altered synthesis or agenesis in one or more globin chains. Families who have a child with thalassemia major face a myriad of significant problems. Hormozgan province ranks second with thalassemic patients in Iran. Therefore, current research is aimed to analyze the reproductive behavior of such families in the southern province of Iran. Methods: In this descriptive study 190 mothers of patients suffering from thalassemia major were included. The reproductive behavior of mothers was investigated by a questionnaire regarding the number of thalassemic infants born after their first child with thalassemia major. Results: About 23% of these mothers had more than 1 child with major thalassemia. The findings showed that the reasons for conception among these mothers were to have a healthy child (64.2%) and to have a boy (20%). In about 92.6% of mothers CVS test was not performed. Conclusion: This study showed that awaring mothers and families regarding the prevention of birth of afflicted infants and provision of accessible diagnostic facilities can reduce the number of children with thalassemia major. [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]

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]