Beta-thalassemia Gene Research Articles

Beta-Thalassemia Haplotypes in Southwest of Iran

Background: Thalassemia is a widespread disease affecting people across various ethnicities and regions. In comparison to previous studies conducted in different regions of Iran, such as those in Lorestan and Sistan-Baluchestan, this study highlights unique mutation patterns prevalent in the southwestern population, emphasizing the genetic heterogeneity in this region. The identification of common mutations of beta-thalassemia in various ethnic groups within the nation is regarded as a practical solution for thalassemia prevention and prenatal diagnosis. Materials and Methods: In this retrospective observational study, the medical records of 545 patients with various types of beta-thalassemia (silent, minor, intermediate, and major), referred to the center at Baqaei 2 hospital over a 14-year period (2008–2022), were examined. The age range of patients spanned from a 2-month-old fetus to a 34-year-old individual. Their mutations and thalassemia types were determined and confirmed using molecular methods, including PCR-ARMS (polymerase chain reaction-amplification refractory mutation system) and sequencing. The results were analyzed using SPSS software. Results: The study examined 545 patients and identified 81 types of mutations. The most frequent mutations observed were CD36-37(-T)/N, IVSII-1/N, and IVS1-110(G>A). The study also noted population heterogeneity, reflected in the wide range of mutations found in the region. Among the patients, 6 had the silent form of beta-thalassemia, 488 had the minor form (464 patients and 24 fetuses), 9 had the intermediate form (8 patients and 1 fetus), and 42 had the major form (26 fetuses and 16 adults). Conclusion: The identification of prevalent beta-thalassemia mutations facilitates disease control and prevention programs and is crucial for the identification of various beta-thalassemia gene mutations. This should be re-evaluated periodically. Observing a wide range of beta-thalassemia genotypes in the southwestern region of Iran suggests gene flow; thus, identifying these genotypes is instrumental in preventing and controlling the disease.

Obstetric and Gynecology Department of RSUD dr. Soedono Provinsi Jawa

Anaemia is a condition in which the number of red blood cells or the haemoglobin concentration within them is lower than normal. Thalassemia is a Mutation of the globin gene can cause changes in the globin chain, e.g. structural haemoglobinopathy or changes in the rate of synthesis or the production ability of certain globin chains. Epidemiological research in Indonesia found that the frequency of the beta thalassemia gene ranges from 3-10%. Case report of patient Mrs. T, 27 years old, HPHT: 01-10-2023, routine ANC examination every month, ANC examination results 18-19 weeks no complaints and laboratory examination results Hb 4.7. Patients with thalassemia beta major and intermediate need to be given regular transfusions and kept their hemoglobin levels above 10 mg/dl. All patients with homozygous thalassaemia should receive folic acid supplements.

Genotype and Phenotype in Pregnant Women with Both Alpha and Beta Thalassemia Mutations Attended at Vietnam National Hospital of Obstetrics and Gynecology

Introduction: The number of studies that explore people with both alpha and beta thalassemia mutations is still low, not only in Vietnam but around the world as well. We conducted this study to explore genotypes and phenotypes of pregnant women who have both alpha and beta thalassemia mutations in comparison to those who don’t have any thalassemia mutations and those who have either alpha or beta thalassemia mutations. Methods: This was a cross-sectional study conducted in the National Hospital of Obstetrics and Gynecology from September 2020 to July 2021 on medical records of 6929 pregnant women who attended the hospital between 2015 and 2021. Mutation analysis was performed by the α-Globin Strip Assay (Vienna Lab, Austria) and Strip Assay MED (Vienna Lab, Austria). Results: There were 18 pregnant women with both alpha and beta thalassemia genes, in which only SEA mutation caused alpha thalassemia and nearly 70% of beta thalassemia was caused by CD26 mutation. In comparison with pregnant women who didn’t have any thalassemia genes, those with both mutations had higher RBC, RDW, HbA2 and lower HGB, HCT, MCV, MCH, MCHC, and HbA1. We only see the statistically significant difference in HbA1 and HbA2 between those with both mutations and those with either alpha or beta thalassemia mutations. Conclusion: In conclusion, our study showed that there were differences in genotype and phenotype between pregnant women with both alpha and beta thalassemia mutations and other types of thalassemia as well as those without thalassemia.

Awareness and practices regarding thalassemia among parents of transfusion dependent beta thalassemia patients registered with Hamza Foundation Peshawar, Pakistan

Thalassemia, a pervasive and chronic condition that impacts an estimated 200 million people worldwide, is predominantly caused by the beta-thalassemia gene, which is found in approximately 3% of the global population. The purpose of this research, which was carried out from June to December 2022 at the Haemophilia Hospital of the Hamza Foundation Welfare Thalassemia, was to evaluate the knowledge and behaviours of guardians of transfusion-dependent beta-thalassemia patients who were registered with the foundation. The findings of the research, which utilised non-probability convenience sampling to select 150 parents, indicated that 38.7% of the parents surveyed were cognisant of thalassemia, whereas permanent treatment was conspicuously unknown to them. Furthermore, it is noteworthy that a substantial proportion (94%) of parents readily shared food, underscoring the criticality of implementing educational and awareness campaigns targeting not only parents but the broader populace in order to rectify the lack of understanding regarding thalassemia. The fact that genetic counselling was availed of by a minuscule proportion (13.3%) of parents underscores a possible avenue for enhancement in comprehensive care approaches.

Splenic abscess, a rare complication in a case of sickle cell thalassemia

Sickle cell disease (SCD) is an inherited autosomal recessive haemoglobinopathy. Sickle cell beta thalassemia is a variant syndrome of SCD characterised by the compound heterozygosity for sickle and beta thalassemia genes. We present a case of 12 year old male child diagnosed case of sickle cell thalassemia at the age of 2 years with complaints of fever, yellowish discolouration of eyes and drowsiness. USG abdomen was done suggestive of splenomegaly, multiple ill-defined, heterogeneously hypo-echoic, areas scattered throughout the splenic parenchyma with no vascularity within likely representing as splenic micro-abscesses. Child was started on antibiotics covering anaerobic and gram-positive organisms (vancomycin, meropenem, amikacin and metronidazole). Currently child is doing well with huge relieve to his symptoms.

A Study of Knowledge, Attitude, and Practice about Thalassemia among the People of Gilgit and Azad Kashmir, Pakistan

Thalassemia, an inherited blood ailment with a 5 to 8% frequency in the beta-thalassemia gene, is a significant health issue in Pakistan, regardless of ethnicity. A study was conducted in Gilgat, Azad Jammu Kashmir, Pakistan, to assess the general public's awareness of the disease. A systematic questionnaire was created, asking 24 questions on awareness. Only 178 participants answered the questionnaire, indicating low knowledge. Those who correctly answered 13-18 questions had average knowledge, while those who answered more than 18 questions had strong knowledge. Of the 178 participants who had heard the term, 5.4% had a "good" level of awareness, 20.6% had average understanding, and 74% had poor understanding. The study revealed that the general population of Gilgit and Azad Jammu Kashmir, Pakistan, had little understanding of Thalassemia.

Prevalence of thalassemia in the Vietnamese population and building a clinical decision support system for prenatal screening for thalassemia

The prevalence of thalassemia among the Vietnamese population was studied, and clinical decision support systems (CDSSs) for prenatal screening of thalassemia were created. A cross-sectional study was conducted on pregnant women and their husbands visiting from October 2020 to December 2021. A total of 10,112 medical records of first-time pregnant women and their husbands were collected. CDSS including two different types of systems for prenatal screening for thalassemia (expert system [ES] and four artificial intelligence [AI]-based CDSS) was built. 1,992 cases were used to train and test machine learning (ML) models while 1,555 cases were used for specialized ES evaluation. There were 10 key variables for AI-based CDSS for ML. The four most important features in thalassemia screening were identified. Accuracy of ES and AI-based CDSS was compared. The rate of patients with alpha thalassemia is 10.73% (1,085 patients), the rate of patients with beta-thalassemia is 2.24% (227 patients), and 0.29% (29 patients) of patients carry both alpha-thalassemia and beta-thalassemia gene mutations. ES showed an accuracy of 98.45%. Among AI-based CDSS developed, multilayer perceptron model was the most stable regardless of the training database (accuracy of 98.50% using all features and 97.00% using only the four most important features). AI-based CDSS showed satisfactory results. Further development of such systems is promising with a view to their introduction into clinical practice.

The beta thalassaemia trait in Jamaica.

The objective of this study was to review the prevalence and features of the beta thalassaemia trait in Jamaican populations. Screening of 221,306 newborns over the last 46 years has given an indication of the distribution and prevalence of beta thalassaemia genes, and screening of 16,612 senior school students in Manchester parish, central Jamaica, has provided their haematological features. The prevalence of the beta thalassaemia trait predicted from double heterozygotes was 0.8% of 100,000 babies in Kingston, 0.9% of 121,306 newborns in southwest Jamaica, and 0.9% of school students in Manchester. Mild beta+ thalassaemia variants (-88 C>T, -29 A>G, -90 C>T, polyA T>C) accounted for 75% of Kingston newborns, 76% of newborns in southwest Jamaica, and 89% of Manchester students. Severe beta+ thalassaemia variants were uncommon. Betao thalassaemia variants occurred in 43 patients and resulted from 11 different variants of which the IVSII-849 A>G accounted for 25 (58%) subjects. Red cell indices in IVSII-781 C>G did not differ significantly from HbAA, and this is probably a harmless polymorphism rather than a form of beta+ thalassaemia; the removal of 6 cases in school screening had a minimal effect on the frequency of the beta thalassaemia trait. Red cell indices in the beta+ and betao thalassaemia traits followed established patterns, although both were associated with increased HbF levels. The benign nature of beta+ thalassaemia genes in Jamaica means that cases of sickle cell-beta+ thalassaemia are likely to be overlooked, and important clinical questions such as the role of pneumococcal prophylaxis remain to be answered.

Status Nutrisi dan Hemoglobin Setelah Pemberian Transfusi pada Penderita Thalasemia

More than 5,000 babies are born suffering thalassemia (beta thalassemia major and beta thalassemia Hb E) annually from around the world and 80% of births occur in developing countries (Kantharaj & Chandrashekar, 2018). In Indonesia alone, the frequency of beta thalassemia genes ranges from 3-10% with 2,500 babies born each year and there are 10,531 more patients experiencing thalassemia (Kemenkes, 2019). The general objective of this study was to identify the relationship between nutritional status and changes in hemoglobin levels after transfusion in children with thalassemia at RSD Gunungjati Cirebon. This research method uses descriptive correlation by using a cross sectional. The sample of this research is thalassemia in Gunung Jati Hospital, Cirebon City, totaling 35 respondents using accidental sampling technique. The instrument used is a data and measurement recapitulation sheet. The nutritional status data recapitulation sheet containing components (gender, age, weight, TB) and measurement of Hb before and after blood transfusion using EasyTouch GCHB, as well as data analysis using the Spearman rank, was carried out on July 4-15, 2022. The results of the univariate analysis of the study This is in the category of good nutritional status as many as 18 respondents (51.4%) and an increase in hemoglobin levels of 18 respondents (51.4%) in thalassemia children at Gunungjati Hospital, Cirebon. The results of this study found that there was no relationship between nutritional status and changes in hemoglobin levels in thalassemia children at RSD Gunungjati Cirebon with a value (p = 0.252 > = 0.05).Suggestions for this study are that families and patients should strive to carry out the education provided by nurses and explore more knowledge related to thalassemia, especially nutritional intake.

Prevalence of Thalassemia in the Vietnamese Population and Building a Clinical Decision Support System for Prenatal Screening for Thalassemia.

The prevalence of thalassemia among the Vietnamese population was studied, and clinical decision support systems for prenatal screening of thalassemia were created. The aim of this report was to investigate the prevalence of thalassemia in the Vietnamese population, building a clinical decision support system for prenatal screening for thalassemia. A cross-sectional study was conducted on pregnant women and their husbands visiting the Vietnam National Hospital of Obstetrics and Gynecology from October 2020 to December 2021. A total of 10112 medical records of first-time pregnant women and their husbands were collected. A clinical decision support system was built, including 2 different types of systems for prenatal screening for thalassemia (an expert system and 4 AI-based CDSS). One thousand nine hundred ninety-two cases were used to train and test machine learning models, while 1555 cases were used for specialized expert system evaluation. There were ten key variables for AI-based CDSS for machine learning. The four most important features in thalassemia screening were identified. The accuracy of the expert system and AI-based CDSS was compared. The rate of patients with Alpha thalassemia is 10.73% (1085 patients), the rate of patients with beta-thalassemia is 2.24% (227 patients), and 0.29% (29 patients) of patients carry both alpha-thalassemia and beta-thalassemia gene mutations. The expert system showed an accuracy of 98.45%. Among the AI-based CDSS developed, the multilayer perceptron (MLP) model was the most stable regardless of the training database (accuracy of 98,5% using all features and 97% using only the four most important features). When comparing the expert system with the AI-based CDSS, the accuracy of the expert system and AI-based models was comparable. The developed expert system for prenatal thalassemia screening showed high accuracy. AI-based CDSS showed satisfactory results. Further development of such systems is promising with a view to their introduction into clinical practice.

The Misdiagnosis of Beta-Thalassemia Heterozygosity Led by Hyperthyroidism

When patients have mild microcytic hypochromic anemia with slightly increased hemoglobin (Hb) A2 fraction, the most likely diagnosis is beta-thalassemia heterozygosity. But herein we found a patient who had all these hematological parameters but did not have beta-thalassemia heterozygosity. He was a 14-year-old Thai who presented with fatigue and heat intolerance for 2 weeks. His physical examination revealed mild diffuse enlargement of thyroid gland. Blood tests showed Hb 120 g/L, mean corpuscular volume (MCV) 72.1 fL, mean corpuscular hemoglobin (MCH) 23.3 pg/cell, free triiodothyronine (FT3) > 20 pg/mL, free thyroxine (FT4) > 5.0 ng/dL, thyrotropin < 2.5 mIU/L, serum ferritin 51.3 µg/L, Hb A2 3.8%. Besides primary hyperthyroidism, he was diagnosed with beta-thalassemia heterozygosity. After being treated with antithyroid drug for 6 months, his blood tests showed subclinical hyperthyroidism, Hb 146 g/L, MCV 83.3 fL, MCH 26.3 pg/cell, Hb A2 3.0%. Not only the thyroid hormones levels but also the Hb concentration, MCV, and the Hb A2 percentage became normal. Due to this inconsistency, the DNA analysis for beta-thalassemia genes was performed and found negative for numerous common and rare beta-thalassemia genes meanwhile beta-globin gene sequencing appeared normal. It should be concluded that hyperthyroidism could induce slightly elevated Hb A2 percentage and mild hypochromic microcytic anemia in a normal individual, leading to the misdiagnosis of beta-thalassemia heterozygosity. In other words, Hb analysis should not be performed during hyperthyroidism and it should be delayed till achievement of the euthyroid stage.

Analysis of Common Beta-Thalassemia (β-Thalassemia) Mutations in East Java, Indonesia.

BackgroundThe frequency of the beta-thalassemia (β-thalassemia) gene in Indonesia ranges from 3 to 10%. However, in the East Java province, there is still limited information on the prevalence of β-thalassemia mutations in clinically diagnosed beta-thalassemia patients of East Java. Therefore, this study aimed to characterize β-thalassemia mutations in selected patients in the East Java province of Indonesia.MethodsThis is an analytical observational study. Diagnosis of β-thalassemia was based on clinical presentation, complete blood count (CBC), and hemoglobin (Hb) electrophoresis. Blood specimens taken from each patient in three ethylenediaminetetraacetic acid (EDTA) tubes were analyzed for CBC and Hb electrophoresis and processed for DNA extraction and subsequent polymerase chain reaction (PCR). Detection of mutations in Hemoglobin Subunit Beta (HBB) gene exons 1–3 of the β-thalassemia gene as the common mutation in Indonesia was done using PCR followed by Sanger sequencing.ResultsIn total, 33 (n = 33) participants were involved in this study with ages ranging from 5 to 17 years comprising 19 women and 14 men. Their ethnic origins were Javanese (n = 30) and Chinese (n = 3). CBC results showed that mean ± standard deviation (SD) for Hb, red blood cell (RBC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and red cell distribution width (RDW)-CV were 81.2 ± 7.0 g/L; 3.40 ± 0.39 × 109/L; 71.05 ± 5.72 fL; 24.12 ± 2.45 pg; 33.91 ± 1.47 g/dl; 24.38 ± 6.02%, respectively. Hb electrophoresis revealed that 5 out of 33 participants had beta-thalassemia and 28 out of 33 participants had hemoglobinopathy (Hb) E/beta-thalassemia. Results of Sanger sequencing showed the following genotype variations in the samples: 12 (36.4%) with βCD26/βIVS−I−5; 6 (18.2%) with βCD26/βCD35; 3 (9.1%) with βCD26/βIVS−I−2; 2 (6.1%) with βCD27/28/βCD40; 2 (6.1%) with βIVS−I−1/βCAP+1; and βCD26/βIVS−I−1; βIVS−I−5/βCAP+1; βIVS−I−5/βCD35; βCD26/βCD37; βCD26/βCD15; βCD26/βCD40; and βIVS−I−5/βCD19 in 1 (3%) sample, respectively, and 1 (3%) had no abnormality detected in sequencing even though electrophoresis showed abnormality in the migration pattern. The βCD26/βIVS−I−5 mutation was found in samples that were noted to have Hb E/beta-thalassemia on Hb electrophoresis.ConclusionThe underlying genetic variations are heterogeneous in thalassemia patients in East Java, where 12 variants were found. The most common variant was βCD26/βIVS−I−5, which all accounted for Hb E/beta-thalassemia on Hb electrophoresis. Furthermore, 28 out of 33 participants had hemoglobinopathy (Hb) E/beta-thalassemia.

Lentiviral vector containing beta-globin gene for beta thalassemia gene therapy

Background and aimBeta thalassemia is a common monogenic disorder caused by partial or complete reduction of beta globin chains synthesis. In recent years allogeneic bone marrow transplantation (BMT) has been considered to be the successful cure for patients with thalassemia major, however this is restricted due to limited number of HLA-matched donors. Therefore, molecular approaches including gene therapy for direct normal beta globin gene transmission seem quite promising to cure thalassemia. The goal of this study was to evaluate the beta globin gene expression in K562 cell line, as a model of hematopoietic cell, transduced with lentiviral vector carrying normal beta globin gene. MethodsFor our purpose, we designed the DEST Lentiviral vector (3rd generation) carrying normal beta globin gene and its promoter and packaged in LentiX-293T cell line. The K562 cell line was transduced by packaged lentivirus containing β-globin cassette (pLenti-HBB). Bulk cells suspension form K562 cells were diluted and seeded into 96-well micro plate by manual pipetting. After single cell expansion, β-globin protein expression level in single cell clones was determined by flowcytometry and Western blotting. ResultsOur results showed that we have successfully packaged and generated lentivirus in LentiX-293T cell line. Flowcytometry analysis showed that beta globin protein expression achieved 20.3% in bulk population of K562 cells in MOI = 20 and 74.4% in F2 clone. ConclusionThese data indicated that vector used in this study is efficient in vitro and could be applied in gene therapy in patient's hematopoietic stem cell. The final goal of this study is to examine designed vector in hematopoietic stem cells promising therapeutic strategy for beta thalassemia and sickle cell disease.

Development and clinical application of a preimplantation genetic testing for monogenic disease (PGT-M) for beta thalassemia in Vietnam

PurposeThe purpose of this research is to study the clinical outcomes using a next-generation sequencing-based protocol allowing for simultaneous testing of mutations in the beta thalassemia (HBB) gene, including single nucleotide polymorphism (SNP) markers for PGT-M along with low-pass whole genome analysis of chromosome aneuploidies for PGT-A.MethodsA combined PGT-M (thalassemia) plus PGT-A system was developed for patients undergoing IVF in Vietnam. Here we developed a system for testing numerous thalassemia mutations plus SNP-based testing for backup mutation analysis and contamination control using next-generation sequencing (NGS). Low -pass next-generation sequencing was used to assess aneuploidy in some of the clinical PGT cases. Patients underwent IVF followed by embryo biopsy at the blastocyst stage for combined PGT-A/M.ResultsTwo cases have completed the entire process including transfer of embryos, while a further nine cases have completed the IVF and PGT-M/A analysis but have not completed embryo transfer. In the two cases with embryo transfer, both patients achieved pregnancy with an unaffected, euploid embryo confirmed through prenatal diagnosis. In the further nine cases, 39 embryos were biopsied and all passed QC for amplification. There were 8 unaffected embryos, 31 carrier embryos, and 11 affected embryos. A subset of 24 embryos also had PGT-A analysis with 22 euploid embryos and 2 aneuploid embryos.ConclusionsHere we report the development and clinical application of a combined PGT-M for HBB and PGT-A for gross chromosome aneuploidies from 11 patients with detailed laboratory findings along with 2 cases that have completed embryo transfer.

Non-invasive prenatal diagnosis for beta-thalassemia by detecting paternal CD41-42 mutation in cell-free DNA derived from maternal plasma with droplet digital PCR

To establish a non-invasive method for beta-thalassemia by detecting parental CD41-42 mutation in cell-free DNA derived from maternal plasma with droplet digital PCR (ddPCR). Beta-actin gene and beta-thalassemia gene CD41-42 mutation were respectively set as the reference and target sequences. A novel method was established based on Bio-Rad ddPCR technique with specific primers and TaqMan probes for the two genes. The accuracy, sensitivity and detective linearity range of the developed method were evaluated by detection of the target gene gradient concentration samples. The applicability was also evaluated by testing 20 maternal plasma samples. The ddPCR method could accurately detect the beta-thalassemia CD41-42 mutation in cell-free DNA derived from maternal plasma. Within the target sequence concentration ratio of 5.00%-0.50%, the relative errors were all < 0.05, the linear regression equation was Y=1.0101-X-0.0071 and R2=0.9994. The results of 20 maternal plasma cell-free DNA samples were all consistent with those of the follow-up testing. A ddPCR method for detecting parental CD41-42 mutation in cell-free DNA from maternal plasma was developed. The method is simple, rapid, accurate, and can be applied for non-invasive prenatal diagnosis for couples simultaneously carrying the CD41-42 mutation.

Report of Beta Thalassemia in Newar Ethinicity

Beta thalassemia trait is a heterogeneous autosomal recessive form of beta thalassemia. Individual with beta thalassemia are clinically asymptomatic. Here we have described a case that has been incidentally diagnosed as beta thalassemia trait. A 31 year old male form Newar Community came to hospital for routine health checkup was send for hematological investigation. On examination, his red cell morphology was found to be microcytic hypochromic and his hemoglobin concentration was mildly decrease. His other parameters was evaluated and requested for analysis of iron profile and hemoglobin electrophoresis. Iron profile test was normal. Hemoglobin electrophoresis showed prominent band in HbA2 region. Presence of HbA2 band was confirmed by hemoglobin variant HPLC analysis. A diagnosis of heterozygous beta thalassemia trait was made. Prevalence of beta thalassemia gene in Tharu population was reported but its presence in other communities is still unknown so it is recommended to study the prevalence of beta thalassemia gene in Newar community as well.

Comparison of Resistance Index and Peak Systolic Velocity of Fetal Middle Cerebral Artery between Normal and Fetuses with Mutated Beta-Thalassemia Gene

Comparison of Resistance Index and Peak Systolic Velocity of Fetal Middle Cerebral Artery between Normal and Fetuses with Mutated Beta-Thalassemia Gene

Thalassemia Spectrum and Prenatal Diagnosis among Voluntary Couples in Shushtar City, during a Five Year Period

Background: Thalassemia and other hemoglobinopathies are inherited disorders that result from genetic defects causing deficient synthesis of hemoglobin polypeptide chains. This study was done to determine the prevalence and to study the complete spectrum of alpha and beta thalassemia gene mutations in the voluntary hemoglobinopathy carrier couples-to-be referred to health centers of Shoushtar city, located in the north Khuzestan province. Methods: Subjects referred to health centers of the city of Shoushtar during 2011 - 2016 were evaluated for the presence of thalassemia minor. After that, alpha and beta thalassemia gene mutations were explored in suspected couples. The samples that underwent PND and diagnosing of causative mutational genes by chorionic villus sampling (CVS) through amniocentesis plus direct or indirect genetic testing at first trimester of pregnancy were proved to be a carrier for alpha thalassemia, beta thalassemia, or other hemoglobinapathies. Results: The mutations for 111/165 (67%) of beta thalassemia chromosomes (19 different mutations) were identified. Of which, IVSII-1 (G > A) and CD 36 - 37 (-T) mutations showed the highest frequency (23.4 for each one) followed by IVSI-110 (G > A) (10%), CD 82-83 (-G) (9%), and -110 (C > T) (7.2%). Among the alpha thalassemia subjects (54/165 (33%)), the -α3.7 mutation was the most common (79/6%) determinant identified in the city of Shoushtar. From 48 voluntary carrier couples who underwent PND, 10 (20.8%) couples were proved to have fetuses with major beta thalassemia; pregnancy termination was done for them. Conclusions: These data suggest that the spectrum of mutations in the city of Shoushtar differs from those reported from other parts of Iran. Therefore, in order to save the time and cost, it is recommended that for the prenatal diagnosis of thalassemia in the city of Shoushtar, analysis of common mutations should be considered as a front line screening strategy. Prenatal diagnosing in this survey demonstrated that beta thalassemia was the most common accounting for all disorders.

Haemoglobinopathies and their occurrence in South East Asia.

A great number of hereditary abnormalities in the rate of haemoglobin synthesis and in structure of haemoglobins are known at the moment. Most of these abnormalities occur only in a few families and are not very important for the health of a population. Some forms occur, however, rather frequently. In Eastern Asia both alfa and beta thalassaemia cases are rather common. The alfa thalassaemia gene seems to occur in a rather high frequency in people from Chinese extraction. The beta thalassaemia gene, too, is not rare in the population of many etnic groups in South- East Asia.The symptoms of homozygocity, heterozygocity and double-heterozygocity for the different thalassaemia genes are described. In most Asia countries genetic abnormalities, causing abnormal haemoglobins, are not as common as they are for instance in many African groups. Forms of Lepore haemoglobin, Hb E, Hb Thai, Hb O, Hb S, have been found in East Asian populations, Hb Thai being rather frequent in Thailand, Hb E in Ceylon.The different clinical pictures of heterozygocity, homozygocity and double-heterozygocity for these genetic abnormalities are described.

A Pilot Study of Noninvasive Prenatal Diagnosis of Alpha- and Beta-Thalassemia with Target Capture Sequencing of Cell-Free Fetal DNA in Maternal Blood.

Thalassemia is a dangerous hematolytic genetic disease. In south China, ∼24% Chinese carry alpha-thalassemia or beta-thalassemia gene mutations. Given the fact that the invasive sampling procedures can only be performed by professionals in experienced centers, it may increase the risk of miscarriage or infection. Thus, most people are worried about the invasive operation. As such, a noninvasive and accurate prenatal diagnosis is needed for appropriate genetic counseling for families with high risks. Here we sought to develop capture probes and their companion analysis methods for the noninvasive prenatal detection of deletional and nondeletional thalassemia. Two families diagnosed as carriers of either beta-thalassemia gene or Southeast Asian deletional alpha-thalassemia gene mutation were recruited. The maternal plasma and amniotic fluid were collected for prenatal diagnosis. Probes targeting exons of the genes of interest and the highly heterozygous SNPs within the 1Mb flanking region were designed. The target capture sequencing was performed with plasma DNA from the pregnant woman and genomic DNA from the couples and their children. Then the parental haplotype was constructed by the trios-based strategy. The fetal haplotype was deduced from the parental haplotype with a hidden Markov model-based algorithm. The fetal genotypes were successfully deduced in both families noninvasively. The noninvasively constructed haplotypes of both fetuses were identical to the invasive prenatal diagnosis results with an accuracy rate of 100% in the target region. Our study demonstrates that the effective noninvasive prenatal diagnosis of alpha-thalassemia and beta-thalassemia can be achieved with the targeted capture sequencing and the haplotype-assisted analysis method.