Screening For Hemoglobinopathies Research Articles

Antenatal screening for haemoglobinopathies: current status, barriers and ethics.

Sickle cell disease (SCD) and thalassaemia are genetic disorders that are caused by errors in the genes for haemoglobin and are some of the most common significant genetic disorders in the world, resulting in significant morbidity and mortality. Great disparities exist in the outcome of these conditions between resource- rich and resource-poor nations. Antenatal screening for these disorders aims to provide couples with information about their reproductive risk and enable them to make informed reproductive choices; ultimately reducing the likelihood of children being born with these conditions. This review provides an overview of the current status of antenatal, pre-marital and population screening of SCD and thalassaemia in countries with both high-and low prevalence of these conditions, methods of screening in use, and discusses some of the pitfalls, ethical issues and controversies surrounding antenatal screening. It also discusses outcomes of some screening programmes and recognises the need for the establishment of antenatal screening in areas where their prevalence is highest; namely sub-Saharan Africa and India.

Screening for Hemoglobinopathies in Pregnant Women

Screening for Hemoglobinopathies in Pregnant Women

Molecular epidemiology, pathogenicity, and structural analysis of haemoglobin variants in the Yunnan province population of Southwestern China

Abnormal haemoglobin (Hb) variants result in the most commonly inherited disorders in humans worldwide. In this study, we investigated the molecular epidemiology characteristics of Hb variants, along with associated structural and functional predictions in the Yunnan province population of Southwestern China. A total of 41,933 subjects who sought haemoglobinopathy screening were included. Based on bioinformatics and structural analysis, as well as protein modeling, the pathogenesis and type of Hb genetic mutations were characterized. Among all individuals studied, 328 cases (0.78%) were confirmed as carriers of Hb variants, with 13 cases (0.03%) presenting α-globin variants, 313 (0.75%) β-globin variants, and two δ-globin variants. A total of 19 different mutations were identified, including three novel mutations. In addition, 48 cases of ααCS mutations and 14 cases of Hb H or Hb Bart’s were found. The isoelectric point, evolutionary conservation, and genotype-phenotype correlation for these mutations were predicted. Additionally, secondary and tertiary protein structure modeling were performed for three selected mutations. In conclusion, the prevalence of Hb variants in the Yunnan population is much higher than other regions of China. Complete characterization of these Hb variants is essential for generating a rational strategy to control the haemoglobinopathies in this region.

Analytical performances of a new automated capillary electrophoresis system in the screening for thalassemias and hemoglobinopathies

Analytical performances of a new automated capillary electrophoresis system in the screening for thalassemias and hemoglobinopathies

Hb Gibbon [β124(H2)Pro→Thr (HBB: c.373C>A, p.P125T)], an Asymptomatic Novel Hemoglobin Variant Detected by Newborn Screening

We describe here a previously unreported hemoglobin (Hb) variant, Hb Gibbon [β124(H2)Pro→Thr (HBB: c.373C>A, p.P125T)] detected by newborn Hb screening in a term male with no family history for hemoglobinopathy or other screening abnormalities. This missense mutation produces a β-globin chain variant that was detected by high performance liquid chromatography (HPLC) methods, but is silent by capillary electrophoresis (CE). DNA sequencing studies revealed that his father was also a heterozygote for this mutation. Neither has abnormalities on complete blood count (CBC) or any symptomatology.

Anaemia in pregnancy.

Anaemia in pregnancy is a common medical condition managed by general practitioners (GPs) in Australia. The aim of this article is to raise awareness of anaemia that occurs in pregnancy, understand its increasing complexities with an expanding migrant population, identify at-risk groups and promote appropriate management. With anaemia reportedly occurring in 25% of women in pregnancy and GPs managing the majority of preconception and early pregnancy care, it is important to have a sound understanding of the aetiology, risks and management options. While iron deficiency anaemia is most commonly seen, a more complex understanding in regard to other causes and haemoglobinopathy screening is required.

Antenatal Screening for Haemoglobinopathies by Using High Performance Liquid Chromatography

Antenatal Screening for Haemoglobinopathies by Using High Performance Liquid Chromatography

Newborn Screening for Sickle Cell Disease and Other Hemoglobinopathies: A Short Review on Classical Laboratory Methods-Isoelectric Focusing, HPLC, and Capillary Electrophoresis.

Sickle cell disease (SCD) and other hemoglobinopathies are a major health concern with a high burden of disease worldwide. Since the implementation of newborn screening (NBS) for SCD and other hemoglobinopathies in several regions of the world, technical progress of laboratory methods was achieved. This short review aims to summarize the current practice of classical laboratory methods for the detection of SCD and other hemoglobinopathies. This includes the newborn screening technologies of high-performance liquid chromatography (HPLC), capillary electrophoresis (CE), and isoelectric focusing (IEF).

Newborn screening in the developing countries.

We review newborn screening (NBS) publications from the developing countries to identify global progress in improving child health. Many developing countries do not yet have national NBS. As infant mortality rates decline, NBS gains in public health priority. Local incidence and outcome data are used to persuade health officials to include screening in priority health spending. Congenital hypothyroidism is the most cost-effective screened condition in most countries. In sub-Saharan Africa, India and some parts of Asia, screening for hemoglobinopathies and glucose-6-dehydrogenase deficiency are also important. Expanded screening for metabolic conditions is most needed in areas of high consanguinity. Screening for hearing disorders and critical congenital heart defects is increasing globally. The largest birth cohorts are India and China, but only China has successful NBS. Reports from completed government research projects in India support initiation of NBS. Government activities around NBS are increasing in India and there is increased emphasis on pilot programs for sickle cell NBS in sub-Saharan Africa. Genetic counseling training in Asia and Africa is increasing and will be helpful as part of NBS. To build successful screening programs, partnerships among health professionals, parents, policy makers and industry stakeholders are essential.

Functional Properties of Hb S and Hb C in Stored Cpda-1 Red Blood Cells Concentrate — a Prospective Study

Most of the 1,300 human hemoglobin (Hb) variants are characterized by normal O2 binding, including here the highly prevalent Hbs S [HBB:c.20A>T; p.Glu6Val] and C [HBB:c.19G>A; p.Glu6Lys]. Hb S and Hb C carriers are generally asymptomatic and might be admitted as blood donors. However, the functional efficiency of these variants in standard blood bags - red blood cells (RBC) concentrates - under the interference of anticoagulant and storage is not well established. In this prospective study, three samples of RBC concentrates (phenotypes AA, AS and AC), with citrate phosphate dextrose adenine (CPDA-1) as anticoagulant, were analyzed for equilibrium tests and compared to fresh Hb A without anticoagulant. The Hb samples were extracted after 48 hours and 35 days of storage and purified by exclusion and ion exchange chromatography (Sephadex G-25 and Amberlite MB-3 columns in Hepes buffer without NaCl). O2 affinity was evaluated by spectrophotometry-tonometry method, by determining the p50 in stripped lysates ([Hb]=70 μM/Heme), in pHs of 6.5, 7.0, 7.5, 8.0 and 8.5, for Bohr effect calculations. Heme-heme cooperativity was determined by Hill coefficient (n) in all studied pHs. The activity of allosteric effector in the Hb-O2 ligation was also tested, using inositol hexaphosphate ([IHP]=1mM), a mimetic compound of the intraerythrocytic 2,3-BPG. The p50 of Hb A after 35 days in stored blood bag was decreased in all pHs, in both presence and absence of IHP, when compared to fresh Hb A, suggesting that the anticoagulant and the storage might affect HbA-O2 binding, increasing its affinity for the ligand. No other differences were observed: heme-heme cooperativity and Bohr effect were similar to fresh Hb A without anticoagulant. The same was found when stored Hb AS was compared to Hb A from blood bag (35 days storage, in the stripped state and under the interference of IHP). However, the stripped lysate containing Hb AC revealed an important reduction of the O2 affinity after both 48 hours and 35 days of storage, mainly at pHs ³ 7, thus interfering in the Bohr effect. The heme-heme cooperativity resulted in normal n coefficients, indicating that the Hb-O2 ligation remained cooperative, in spite of the significant reduction of O2 affinity. Similar results were observed in the presence of IHP (48 hours and 35 days), although Bohr effect was reestablished, indicating that the supplementation with a 2,3-BPG-like allosteric effector might restore some Hb-ion interactions, and therefore, Hb C function. As the 2,3-BPG is consumed with storage of RBC concentrates, Hb AC showed an even lower affinity for O2 after 35 days of storage. Although still preliminary, our results indicate a significant functional reduction of Hb C in RBC concentrates in standard blood bag (CPDA-1 anticoagulant), proportional to the time of storage. Considering that the screening for hemoglobinopathies in the blood banks routine is mainly focused in the detection of Hb S, a greater understanding about the properties of native Hb and its most frequent variants in stored RBC concentrates could also contribute with the determination of safe parameters in hemotherapy based on the functional efficiency of each hemoglobin. Financial Support: Fapesp, CNPq, Capes, Faepex-Unicamp. DisclosuresNo relevant conflicts of interest to declare.

Increasing Incidence and Prevalence of Pathologic Hemoglobinopathies Among Children in Ontario, Canada from 1991-2013

Abstract Background: In Ontario, Canada's largest province, population-based health administrative data represents an accessible and useful tool for population surveillance of people with chronic diseases. While hemoglobinopathies can be identified using data from universal hemoglobinopathy screening, which was implemented in November 2006, these data would not contain information on affected immigrants (21.9% of the population). We validated algorithms using provincial health administrative data and newborn screening data to identify children with hemoglobinopathies whether or not they were born in Ontario, thereby creating a population-based surveillance cohort. Objectives: (1) Validate algorithms to identify children with sickle cell disease, thalassemia and other hemoglobinopathies from within health administrative data; and (2) Determine incidence and prevalence of hemoglobinopathies in Ontario children. Methods: For the validation study, a positive reference cohort was established using lists of known hemoglobinopathy patients who were followed at five pediatric hemoglobinopathy treatment sites in Ontario and born between November 24, 2006 and March 31, 2013. Health card numbers of these patients were linked deterministically to unique identification numbers in administrative data, which included data on hospitalizations, physician claims, sociodemographic characteristics, immigration records and cause of death. The negative reference cohort included all children residing in Ontario cities who had never been seen at a hemoglobinopathy centre, and therefore assumed not to have disease. Various combinations of administrative data codes were tested for their ability to identify children <18 years of age with hemoglobinopathies from within the databases, and we selected the algorithms with the highest positive predictive value, while maintaining sensitivity >80%. Using two validated algorithms, we identified all children with hemoglobinopathies born between April 1, 1991 and March 31, 2013. We described the crude incidence and prevalence per 100,000 patient-years (PYs). Results: Two algorithms functioned best to identify incident and prevalent hemoglobinopathy cases (see Table). Among children born between April 1, 1991 to March 31, 2013, 1526 incident hemoglobinopathy patients were identified using Algorithm 1 (crude incidence of 4.85 per 100,000 PYs) and 1660 new hemoglobinopathy patients were identified using Algorithm 2 (crude incidence 5.28 per 100,000 PYs, 95% CI 3.51 to 3.92). In 2013, the overall prevalence of children <18 years living with hemoglobinopathies was 1215-1325 cases. Conclusion: Through an innovative approach using provincial health administrative, immigration and demographic data, this study identified a rising incidence and prevalence of hemoglobinopathies among Ontario children <18 years of age between April 1, 1991 and March 31, 2013, potentially due to increased immigration rates. These findings could be used to inform health services distribution. This surveillance cohort will be used to understand the impact of immigration status on health care inequality for hemoglobinopathy-related health services delivery, as well as to assess outcomes in this important group of chronic diseases. Disclosures Klaassen: Amgen Inc.: Membership on an entity's Board of Directors or advisory committees; Octapharma AG: Consultancy, Honoraria; Agios Pharmaceuticals Inc.: Consultancy; Novartis: Research Funding; Hoffman-La Roche: Consultancy; Shire: Consultancy; Cangene: Research Funding. Jardine:Pfizer: Other: Advisory board; Bayer: Other: Advisory board; Baxalta: Other: Advisory board.

Predictors of Hydroxyurea Use in Children with Sickle Cell Disease

Background: Since hydroxyurea emerged as an effective therapy for sickle cell disease (SCD), there have been numerous studies that have demonstrated its safety and efficacy in children and adults with SCD. In their 2014 guidelines, the NHLBI recommended that hydroxyurea treatment should be offered to all infants and children with sickle cell anemia (HbSS and HbS/beta0 thalassemia) starting at 9 months of age. However, hydroxyurea is underused among children and adolescents with SCD and to date, there have been no studies that have identified the specific determinants that may predict hydroxyurea adherence in these patients.Objectives: 1. To identify predictors of hydroxyurea adherence in children with SCD. 2. To measure the rate of hydroxyurea use among CHEO patients with SCD who were born between January 1, 2003 and December 31, 2015; and 3. To compare the rates of SCD-related complications between patients who were not prescribed hydroxyurea, patients who were adherent to hydroxyurea and patients who were not adherent to hydroxyureaMethods: We extracted medical chart data to identify patients with SCD who were born between January 1, 2003 and December 31, 2015. Patients were classified as either “Not prescribed hydroxyurea” or “Prescribed hydroxyurea” based on clinical documentation and the presence of at least one hydroxyurea outpatient prescription. For those patients who were prescribed hydroxyurea, hematological indices were collected and analyzed over time to estimate adherence to hydroxyurea. To measure the adherence of children prescribed hydroxyurea, we examined the trends in the patient's hematological indices after their first prescription of hydroxyurea. Adherence was defined as increased hematological indices (from baseline) by greater than or equal to any 2 of the following: Mean corpuscular volume (MCV) by 10 fL; Hemoglobin levels (g/L) by 10 g/L and/or %HbF (fetal hemoglobin) by 10%. We measured the frequency of disease-related complications among CHEO patients with SCD according to their use of hydroxyurea and used multivariate analyses to evaluate immigration status, newborn screening status, SCD subtype, SCD complications, income, age and sex as predictors for hydroxyurea adherence.Results: Children with HbSS were more likely to have been prescribed hydroxyurea compared to children with HbSC (87.8% vs. 9.5%). Canadian citizenship, newborn hemoglobinopathy screening and lower familial income were associated with better hydroxyurea adherence (Table 1). Although the association was not statistically significant, patients were more likely to be prescribed hydroxyurea if they were from a lower income background (61.9% for lowest and second lowest quartiles vs. 38.1% for third and highest quintiles). Patients were also more likely to adhere to hydroxyurea if they did not have private medical insurance for hydroxyurea coverage (Table 1). Finally, hydroxyurea adherence was associated with reduced rates of health care utilization and SCD-related complications (Table 2).Conclusions: In line with previous studies of hydroxyurea for the treatment of SCD, patients who were adherent to hydroxyurea had fewer complications compared to those patients who were either non-adherent to or not prescribed hydroxyurea. Similarly, patients had fewer complications after being prescribed hydroxyurea compared to before they started hydroxyurea with a reduction in the rate of ED visits, acute chest syndromes, complications, transfusions and hospitalizations. Patients from non-immigrant families, patients who were identified through newborn hemoglobinopathy screening and patients from lower income families were more likely to be adherent to hydroxyurea. Although the results of this study were limited by its small sample size, further studies will clarify these determinants of hydroxyurea adherence among SCD patients and enable clinicians to improve hydroxyurea adherence for SCD patients. DisclosuresKlaassen:Shire: Consultancy; Novartis: Research Funding; Hoffman-La Roche: Consultancy; Amgen Inc.: Membership on an entity's Board of Directors or advisory committees; Octapharma AG: Consultancy, Honoraria; Agios Pharmaceuticals Inc.: Consultancy; Cangene: Research Funding.

Antenatal Screening for Hemoglobinopathies with HPLC

Introduction: Hemoglobinopathies are the most commonly encountered monogenic disorders of blood in Southeast Asia and Indian subcontinent. Screening of individuals at increased risk of being carriers for thalassemia and hemoglobinopathies, can identify couples with a 25% risk of having a pregnancy with a significant genetic disorder, for which prenatal diagnosis is possible. This study is done to know the prevalence of hemoglobinopathies and variant of haemoglobin using cation exchange high performance liquid chromatography (CEHPLC). Materials and Methods: 2 ml of venous blood was collected in EDTA vials from the pregnant mothers after informed consent. The blood was subjected to complete hemogram, peripheral blood smear and HPLC using Variant Hemoglobin Testing System (BioRad Laboratories). Beta Thalassemia short programme was used. Descriptive analysis was done and data is presented in numbers and percentages. Results: 467 blood samples from various ethnic groups were evaluated. 70 (14.99%) samples showed features of hemoglobinopathies by HPLC. There were 46 (9.85%) cases of HbE heterozygous,12 (2.57%) cases of HbE homozygous, 9(1.93%) cases of Beta Thalassemia Trait, 2 (0.43%) cases of double heterozygous and 1 (0.21%) case of Hb-D Iran. Conclusion: This study showed a high prevalence of hemoglobinopathies in antenatal mothers necessitating an appropriate screening strategy for antenatal mothers. We also concluded that HPLC is a sensitive technique for studying hemoglobinopathies during pregnancy and may be utilized for screening.

A transition in haemoglobinopathy screening within a tertiary care centre

A transition in haemoglobinopathy screening within a tertiary care centre

Comparative analysis of the role of isoelectric focusing and high-performance liquid chromatography in newborn screening in hemoglobinopathies

Introduction: Hemoglobinopathies are the common genetic disorders and are considered as the emerging health burden. To reduce the childhood and infant mortality and morbidity, early recognition by newborn screening and timely intervention is necessary. Objectives: The objectives of this study are to evaluate the prevalence of different hemoglobinopathies in the study population and to compare the efficacy of isoelectric focusing (IEF) and high-performance liquid chromatography (HPLC) tests in the neonatal screening for hemoglobinopathies. We have also assessed the predominant mutations for all ?-thalassemia variants. Materials and Methods: The prospective observational study was conducted in the Department of Pathology in collaboration with the Department of Neonatology over 1½ years including 4200 neonates. Both IEF and HPLC diagnoses were attempted and compared with recall HPLC and parent HPLC. DNA analysis was also done further confirmation in all thalassemia cases. Results: A total of 213 cases with 11 Hb variants were detected; among them, HbE trait was the most prevalent type. Overall sensitivity, specificity, and negative and positive predictive values were noted. The results of IEF were comparable with HPLC with a statistically significant measure of agreement of ?=0.928 between the two. DNA analysis of 37 ?-thalassemia variants revealed three common mutations, i.e., cd26 (G>A), IVS1-5 (G>C), and cd15 (G>A). Conclusion: In IEF, the hemoglobin separation is very precise with little band overlap, but the process and interpretation need a high expertise. Due to more sensitivity, IEF should be the initial screening test followed by recall HPLC for confirmation of the diagnosis.

380. Adherence to a selective antenatal haemoglobinopathy screening policy within a tertiary level obstetric unit in Australia

There is no national Australian antenatal haemoglobinopathy screening policy and a previous Australian study of antenatal haemoglobin electrophoresis requests highlighted poor patient selection. Whilst benefits of screening have been well demonstrated, adherence to selective screening protocols in low prevalence populations has not been well described. This study aims to assess adherence to an established selective antenatal screening policy within a low prevalence Australian population. This single-centre retrospective cohort study identifies all women attending for routine public antenatal care with estimated due date between 1st January 2014 and 31st December 2016 who meet criteria for selective screening on the basis of established guidelines. The primary outcome was the proportion of eligible women who were appropriately screened. Secondary outcomes included rates of partner testing and rates of specialist referral where fetal risk was identified. A total of 11,709 births were recorded during the study period. Eligibility for screening was identified on the basis of ethnicity in 1076 (9.1%), abnormal red cell indices in 427 (3.6%) and known personal or family history in 77 (0.6%). 158 (10%) had haemoglobin electrophoresis results documented during the antenatal course with 64 (4%) initiated by obstetric staff during the index pregnancy at a median gestation of 22 weeks. Partner testing was documented in 140 (88.6%) of “at risk” pregnancies and of these, appropriate specialist referral was indicated in 28 (20%) but occurred in only 17. This is the first Australian study to describe the rate of pregnancies meeting established criteria for selective screening in a low prevalence population. This data demonstrates poor identification of “at risk” patients leading to limitation of informed choice for affected families. The demonstration of poor adherence within the clinical setting supports arguments for universal screening which becomes increasingly cost effective as the selective screen failure rate rises.

Awareness and Attitude of University Students About Screening and Testing for Hemoglobinopathies: Case Study of the Aseer Region, Saudi Arabia

Hemoglobinopathies can disturb a patient’s life style leading to community problems. Premarital screening is an important tool to control and minimize hemoglobinopathies. This study aimed to assess and improve the awareness and attitude of King Khalid University (KKU) [Abha, Kingdom of Saudi Arabia (KSA)] students in the Aseer Region, regarding hemoglobinopathies and the National Premarital Screening Programme (NPMS) in addition to screening for hemoglobin (Hb) variants of students who agreed to participate. This study was an interventional educational prospective study of electronic-lectures (e-lectures) that addressed some important issues of hemoglobinopathies and premarital screening. Six hundred and eleven students were interviewed during the academic year 2017/2018, using closed-ended questionnaires that distributed before and after intervention. Blood samples were taken from 114 students who agreed to check their Hb type by the D-10 Hemoglobin Testing System. The results revealed significant changes in knowledge and attitude of students toward hemoglobinopathies and premarital counseling after intervention. These results reflected the need for easily accessible and continuous health education programs for students to increase their awareness and attitude toward hemoglobinopathies. Laboratory results for 114 students revealed seven cases with microcytic hypochromic anemia (6.1%); they were all females. Blood screening for Hb variants revealed another two females (1.75%) with sickle cell trait (Hb AS). Electronic-health (E-health) is an efficient tool for improving the awareness and attitude of the community toward hemoglobinopathies. Screening blood tests for detection of hemoglobinopathies should be provided to young adults at an earlier stage (before marriage) to decrease the incidence of hereditary diseases in the community.

Study of High Performance Liquid Chromatography and Turbidimetric Inhibition Immunoassay for HbA1c Analysis in Diabetic Patients with Variant Hemoglobin

Background: HbA1c is considered as “gold standard” to evaluate glycemic control in patients with diabetes. Hemoglobin variants are mutant forms of hemoglobin that can occur by genetic changes in specific amino acid that can affect the accuracy of HbA1c measurements. High performance liquid chromatography (HPLC) is the standard method for HbA1c but inaccurate HbA1c values can occur when hemoglobin variants are present in diabetic patient. The aim of our study is to see Turbidimetric Inhibition Immunoassay (TINIA) method can report HbA1c values in diabetic patients with variant hemoglobin when the values are inaccurate on HPLC.Methods: 7590 diabetic patients were analyzed for HbA1c by HPLC method from BIRDEM General Hospital during December 2013 to January 2014. HbA1c levels were again measured by TINIA method in 50 cases out of 7590 who showed either undetectable / below normal HbA1c levels. Hb electrophoresis confirmed the variant hemoglobin in few casesResults: 50 cases out of 7590 (0.65%) had either undetectable / below normal HbA1c levels by HPLC method. Males-26 and females-24; and the ratio was 0.92:1. In 27 cases, HbA1c values were undetectable by HPLC method but in the reportable range by TINIA method. In the other 23 cases, HbA1c levels were below the reportable range (<4%) by HPLC method but were in the normal or higher range by TINIA method. On Bland Altman plot, TINIA method did not agree with HPLC method in variant cases.Conclusion: In South East Asia where Hb variant is high, Low or undetectable HbA1c level by HPLC may be a convenient clue for screening of hemoglobinopathies especially among diabetic population in Bangladesh. All laboratories should have alternative method of HbA1c testing like TINIA along with HPLC for correct determination of glycemic control in variant casesBirdem Med J 2018; 8(2): 114-117

Mutation Screening of the Krüppel-like Factor 1 Gene in Individuals With Increased Fetal Hemoglobin Referred for Hemoglobinopathy Investigation in South of Iran.

Any mutation in the Krüppel-like factor 1 (KLF1) gene may interfere with its proper related function in the erythropoiesis process and lead to alterations in proper activation of its downstream protein through globin switching, which results in an increase in fetal hemoglobin (HbF). This study aimed to investigate whether KLF1 mutation can associate with high level of HbF in individuals with increased fetal hemoglobin referred for screening of hemoglobinopathies in south of Iran. The human KLF1 gene was amplified via the polymerase chain reaction procedure, and sequencing was used to determine any mutation in these patients. Moreover, XmnI polymorphisms in the position of -158 of γ-globin gene promoter were analyzed in all patients by polymerase chain reaction restriction fragment length polymorphism. Analysis of sequencing revealed a missense mutation in the KLF1 gene, p.Ser102Pro (c.304T>C), which was detectable in 10 of 23 cases with elevated HbF level. This mutation was only detected in individuals who had a HbF level between 3.1% and 25.6%. Statistical analysis showed that the frequency of C allele is significantly correlated with a high level of HbF (P<0.05). The allele frequency of positive result of XmnI polymorphism in individuals with increased HbF level was also significant, which showed an association with increased HbF level (P<0.05). To the best of our knowledge, this is the first report of p.Ser102Pro (c.304T>C) in the KLF1 gene in β-thalassemia patients with increased level of fetal hemoglobin. According to statistical results of p.Ser102Pro mutation and XmnI polymorphism, it has been strongly suggested that both polymorphisms have an association with increased HbF samples. These nucleotide changes alone may not be the only elements raising the level of HbF, and other regulatory and modifying factors also play a role in HbF production.

Haemoglobinopathy screening in pregnancy

Background: Haemoglobinopathies are the most common recessive monogenetic disorders worldwide, with an increasing prevalence of carriers in Australia as migration patterns change. The ideal algorithm for screening is yet to be determined, as screening guidelines from other populations do not reflect the ethnic diversity of the Australian population.