Α-thalassemia Genotypes Research Articles

Clinical value of PCR-flow Fluorescence Hybridization in Prenatal Genetic Diagnosis of Thalassemia

To explore the value of PCR-flow fluorenscence immunmicrobeads assay in prenatal gene diagnosis of thalassemia. A total of 1001 pregnant women and their couples checked in the First Affiliated Hospital of Sun Yat-Sen University from January 2016 to August 2019 were selected. Both pregnant women and their spouses were the carriers of thalassemia gene. Samples such as amniotic fluid, were used to extract genomic DNA at the right time. Parallel detection of α- and β- thalassemia genes to samples should be carried out by PCR-flow cytometric fluorescence hybridization and traditional multiple Gap-PCR and PCR-RDB techniques. The consistency of two methods in gene diagnosis of thalassemia was evaluated by analyzing the results of detection. 389 normal genotypes (38.86%, 389/1001) and 59 abnormal genotypes (61.14%, 612/1001) was cheked out by the two methods, including 416 cases of α-thalassemia, 162 cases of β-thalassemia and 34 cases of αβ- complex thalassemia. The main genotypes of α-thalassemia were --SEA, -α3.7 and -α4.2. The mutation frequency of CD41-42 was the highest among the β-thalassemia genotypes, which followed by IVS-II-654 and CD17. A rare HKαα/--SEA thalassemia genotype was detected. Compared the traditional multiple Gap-PCR and PCR-RDB techniques, the sensitivity, specificity, positive predictive value, negative predictive value and total consistent rate of PCR-flow fluorenscence immunmicrobeads assay were 100%, which showed that the two methods were completely consistent. Guangzhou is a area with high incidence of thalassemia, and the genetic types of thalassemia are complex and diverse. Prenatal diagnosis is the final barrier to the prevention of thalassemia. PCR flow-cytometric fluorescence hybridization, as a simple and fast technique, combined with traditional techniques in parallel contributed to the accuracy of prenatal gene diagnosis of thalassemia.

A Nested Asymmetric PCR Melting Curve Assay for One-Step Genotyping of Nondeletional α-Thalassemia Mutations

A rapid DNA-based assay is essential for clinical diagnosis and mass screening in thalassemia-prevention programs. Because of high homology and guanine-cytosine-rich and complex second structure of α-globin genes, it is rather difficult to develop a feasible and simple method for α-thalassemia genotyping. In this study, a strategy of nested asymmetric PCR melting curve analysis was designed to tackle these factors and ensure sensitivity and accuracy. Herein, a novel one-step assay for genotyping of nondeletional α-thalassemia mutations, including hemoglobin (Hb) Westmead (HBA2: c.369C>G), Hb Quong Sze (HBA2: c.377T>C), Hb Constant Spring (HBA2: c.427T>C), CD30 (HBA2: c.91-93delGAG), and CD31 (HBA2: c.95G>A) in a single closed tube, was established and evaluated. All five mutations were accurately determined with the concordance rate of 100% in a blind analysis of 255 genotype-known samples and 1250 clinical samples. In conclusion, this assay is useful for rapid and reliable genotyping of nondeletional α-thalassemia mutations in clinical practice. Especially, the strategy may have the potential to be a versatile scheme for rapid genotyping of other gene mutations because of its high throughput, sufficient stability, low cost, and simple operation.

Diagnosis and Prenatal Diagnosis in a Chinese Family Carrying the Rare α-Thalassemia Gene HBA2: c.1A>G Mutation

The aim of this study was to identify the rare thalassemia genotype in a family and perform prenatal diagnosis (PND) on the proband’s unborn child. Peripheral blood was collected from the family members for hematology analysis and capillary electrophoresis (CE) analysis. Peripheral blood and cord blood were analyzed by gap-polymerase chain reaction (gap-PCR), reverse dot-blot and Sanger sequencing for genotypes of α-thalassemia (α-thal). A heterozygous mutation, HBA2: c.1A>G, was identified in the proband and his father. Two compound heterozygous variants, HBA2: c.1A>G and the – –SEA (Southeast Asian) deletion, were revealed in the proband’s unborn child. The hemoglobin (Hb) CE result of the fetal cord blood indicated the fetus had Hb H disease. We have identified a rare thalassemia mutation (HBA2: c.1A>G) in a Chinese family and enriched the rare α-thal gene pool in the Chinese population. When the patient’s phenotype does not match the genotype detected by thalassemia gene detection kits, further investigation of rare genotypes should be conducted to avoid missed diagnosis or misdiagnosis, which can help guide clinical diagnosis, population screening and genetic counseling.

Analysis on the Genotype of 5018 Cases of Thalassemia in Hunan Area

To investigate the type and distritution of thalassemia gene mutaitons in Hunan area, so as to provide evidence for prenatal screening, diagnosis and reduction of birth defects. A total of 5018 cases from Maternal and Children Health Hospital of Hunan from June 2017 to Dec 2018 were undergone thalassemia gene mutation analysis. The reverse dot blot hydridization was used to detect 6 kinds of genotypes of α-thalassemia and 17 kinds of point mutations of β-thalassemia, and the detected data were analyzed statistically. 889 cases (55.9%) of α-thalassemia carriers were found, including 385 cases of silent α-thalassemia, 488 cases of α-thalassemia trait, 16 cases of Hb H disease. --SEA/αα was the most common genotype in α thalassemia. 664 cases (41.7%) were diagnosed as β-thalassemia carriers, heterozygotes accounted for 99.8% (663/664), IVS-Ⅱ-654, CD41-42M and CD17M were the main genotypes, and compound heterozygote accounted for 0.2% (1/664). 38 cases were diagnosed as α-thalassemia combined β-thalassemia. The constituent ratio of thalassemia gene mutations in Hunan has regional characteristics, --SEA/αα is the most common genotype in α-thalassemia carrier. IVS-Ⅱ-654, CD41-42 and CD17 are common ones in β-thalassemia. The frequency of α-thalassemia combined with β-thalassemia is high.

Analysis on the Genotype of 5018 Cases of Thalassemia in Hunan Area

To investigate the type and distritution of thalassemia gene mutaitons in Hunan area, so as to provide evidence for prenatal screening, diagnosis and reduction of birth defects. A total of 5018 cases from Maternal and Children Health Hospital of Hunan from June 2017 to Dec 2018 were undergone thalassemia gene mutation analysis. The reverse dot blot hydridization was used to detect 6 kinds of genotypes of α-thalassemia and 17 kinds of point mutations of β-thalassemia, and the detected data were analyzed statistically. 889 cases (55.9%) of α-thalassemia carriers were found, including 385 cases of silent α-thalassemia, 488 cases of α-thalassemia trait, 16 cases of Hb H disease. --SEA/αα was the most common genotype in α thalassemia. 664 cases (41.7%) were diagnosed as β-thalassemia carriers, heterozygotes accounted for 99.8% (663/664), IVS-Ⅱ-654, CD41-42M and CD17M were the main genotypes, and compound heterozygote accounted for 0.2% (1/664). 38 cases were diagnosed as α-thalassemia combined β-thalassemia. The constituent ratio of thalassemia gene mutations in Hunan has regional characteristics, --SEA/αα is the most common genotype in α-thalassemia carrier. IVS-Ⅱ-654, CD41-42 and CD17 are common ones in β-thalassemia. The frequency of α-thalassemia combined with β-thalassemia is high.

Molecular analysis of α-thalassemia and β-thalassemia in Quanzhou region Southeast China

AimsThalassemia is one of the most prevalent inherited disorders in south China. However, there still has no comprehensive research on molecular characterisation of α-thalassemia and β-thalassemia in the Quanzhou region...

Molecular characterization of thalassemia and hemoglobinopathy in Southeastern China

Thalassemia and hemoglobinopathy are two common inherited disorders, which are highly prevalent in southern China. However, there is little knowledge on the genotypes of thalassemia and hemoglobinopathy in Southeastern China. In this study, we present a large-scale genetic detection and molecular characterization of thalassemia and hemoglobinopathy in Fujian province, Southeastern China. A total of 189414 subjects screened for thalassemia were recruited, and the hemoglobin components and levels were investigated. Furthermore, suspected common thalassemia was identified, and the suspected rare forms of common thalassemias and hemoglobinopathy were detected. Among the total subjects screened, the overall prevalence of thalassemia and hemoglobinopathy was 6.8% and 0.26%, and rare α-thalassemia genotypes HKαα, –THAI/αα and −α27.6/αα, and novel β-thalassemia gene mutations CD90(G → T) and IVS-I-110(G > A) were identified. Additionally, Hb Q-Thailand hemoglobinopathy and five other types of hemoglobinopathies (Hb New York, Hb J-Bangkok, Hb G-Taipei, Hb G-Coushatta and Hb Maputo) were found. The results of this 10-year large-scale study demonstrate high prevalence of thalassemia with complicated gene mutations in Southeastern China, which provides valuable baseline data for genetic counseling and prenatal diagnosis. In addition to detection of common thalassemia genes, detection of rare thalassemia genotypes and hemoglobinopathies is recommended.

Polymorphisms of α-Globin Genes Compromise Polymerase Chain Reaction-Based α-Thalassemia Genotyping in Three Chinese Families

In practice, gap-polymerase chain reaction (gap-PCR) and reversed dot-blot are the two most frequently used molecular diagnostic methods for α-thalassemia (α-thal) genotyping. Here, we describe three Chinese individuals from three unrelated families in whom a polymorphism on the α-globin gene cluster led to diagnostic pitfalls. During general molecular diagnosis of thalassemia, three individuals with unexplained results were found. Blood or chorionic villus samples were collected from these three individuals and their family members. Hematological investigations and genetic tests were performed. In Family 1, a polymorphism of HBA2: c.301-24delinsCTCGGCC at the annealing site of the forward primer used in the PCR-reverse dot-blot assay was identified, leading to allele drop-out during the PCR amplification process. In Family 2, a synonymous mutation of C>T substitution at codon 125 of the α2 gene (HBA2: c.376C>T) was identified, leading to the failure of PCR-reversed dot-blot for the HBA2: c.377T>C (Hb Quong Sze or Hb QS) mutation. In Family 3, the size of the PCR fragment from the α2-globin allele carrying the HBA2: c.-771_-428del mutation was smaller and nearly equal to the size of the fragment corresponding to the –α4.2 (leftward) deletion; we also found that the HBA2: c.-771_-428del mutation was linked to a known HBA1: c.-673A>G mutation in this family. In conclusion, diagnostic errors may be caused by technical pitfalls or inherent properties of the DNA sample. All logical steps should be taken to monitor and thus preclude such events.

First Report of α-Thalassemia Genotypes from Transcaucasia

Background: Transcaucasia is a geographical region located on the border of Eastern Europe and Western Asia including territories of Azerbaijan, Georgia and Armenia. The region has long been known for high incidence of thalassemia and previous studies reported the highest prevalence of β-thalassemia in Azerbaijan (AZE - 4-5%, GEO - 3%, ARM - 2%) and an overlapping mutation spectrum within the region. Nevertheless, the characteristic genotypes and mutation spectrum of less recognised α-thalassemia have not been reported by far. In this multicentre cross-sectional study, we analysed the genotypes of α-thalassemia patients from Azerbaijan as representative of the region.Methods: 45 patients diagnosed with HbH disease, β-thalassemia major with milder clinical manifestations or any other clinical condition with possible inheritance of α-thalassemia mutations were included in the study. Clinically significant deletions as well as point mutations located on the HBA1 and HBA2 genes were identified via reverse dot blot hybridization method.Results: From total 8 identified mutations, 20.5 kb (45.3%) and 3.7 kb (31.4%) deletions were the most prevalent. Accordingly, -α3.7 /-(α)20.5 genotype was identified in more than half of the patients with HbH disease (N=23). The most common point mutations were α2 Poly A-2 (HBA2:c.*96G>A) - 7.0%, α2 codon 142 [T>C] (HBA2:c.427T>C) - 4.7%, and α2 IVS-I 5nt del (HBA2: c.95+2_95+6delTGAGG) - 4.7%.Conclusion: Deletions with less severe clinical presentation comparing to point mutations accounted for the majority of the spectrum. The milder phenotype might be the reason why this disease has been undermined in the region by β-thalassemia. The spectrum of mutations were similar of the populations of neighbouring high incidence territories such as Iran and Turkey. DisclosuresNo relevant conflicts of interest to declare.

Molecular analysis of hemoglobinopathies in a large ethnic Hakka population in southern China.

Thalassemia is an inherited autosomal recessive disorder with microcytic hypochromic anemia resulting from reduced or absent synthesis of 1 or more of the globin chains of hemoglobin. This study provided the insight into prevalence and molecular characterization of thalassemia in Hakka population. 14,524 unrelated subjects were included in our study from January 2015 to November 2017. All the subjects were detected by hematological analysis, hemoglobin electrophoresis analysis, and molecular diagnosis (gap-polymerase chain reaction and flow-through hybridization technology). Data analysis was used to compare allele frequencies between the Hakka populations. Seven thousand four hundred twenty-two cases of microcytosis were found. The percentage of microcytosis in Meizhou, Ganzhou, and Heyuan was 50.91% (6738/13,236), 51.27% (445/868), and 56.90% (239/420), respectively. A total of 5516 mutant chromosomes were identified, including 3775 α-thalassemia and 1741 β-thalassemia. --SEA/αα was the most common α-thalassemia genotype, followed by -α3.7/αα and -α4.2/αα, accounted for 84.92% of α-thalassemia genotypes. Twelve kinds of mutations and 26 genotypes in β-thalassemia were found. IVS-II-654(C→T), CD41-42(-TCTT), −28(A→G), and CD17(A→T) alleles accounted for 92.65% of these mutations. IVS-II-654/N, CD41-42/N, -28/N, CD17/N genotypes accounted for 91.53% of β-thalassemia genotypes. 27 fetuses with at-risk pregnancies were subjected to prenatal diagnosis. Five fetuses were Bart's hydrops syndrome and 2 fetuses with β-thalassemia major. There were some differences in molecular characterization of thalassemia among Hakka people in different areas of southern China. Our results enriched the related information of thalassemia in the region, which provided valuable references for the prevention and control of thalassemia.

Invasive prenatal diagnosis of α-thalassemia to control Hb Bart's hydrops fetalis syndrome: 15years of experience.

The aim of the present study was to report experiences with invasive prenatal diagnosis of α-thalassemia for the prevention of Hb Bart's hydrops fetalis syndrome in the Guangxi Zhuang Autonomous Region, China. Pregnant women and their partners who tested positive for α0-thalassemia or were diagnosed with HbH diseases were counseled and suggested to undergo a prenatal diagnostic procedure for α-thalassemia. Fetal material was obtained by chorionic villus sampling (CVS) between 9 and 13weeks of gestation, by amniocentesis between 16 and 24weeks of gestation and by cordocentesis after 24weeks of gestation. The α0-thalassemia gene types were detected by gap polymerase chain reaction (Gap-PCR). All results were finally confirmed by DNA analysis after delivery or termination of pregnancy. An invasive prenatal α-thalassemia diagnosis was performed in 3155 cases at risk for Hb Bart's hydrops fetalis syndrome at our hospital from 2002 to 2016. CVS was performed in 1559 cases (49.4%), amniocentesis in 1240 cases (39.3%) and cordocentesis in 356 cases (11.3%). In total, 786 fetuses were diagnosed as Hb Bart's hydrops fetalis syndrome. Among these cases, the α-thalassemia genotype was --SEA/--SEA in 784 cases and --SEA/--THAI in 2 cases. All affected pregnancies were terminated in time. This extensive experience suggests that carrier screening, molecular diagnostics, genetic counselling, and prenatal diagnosis are effective measures to prevent Hb Bart's hydrops fetalis syndrome.

Prevalence and Genotype Analysis of Newborn α-Thalassemia in Wuhan Area of China

To investigate the genotypes of newborn α-thalassemia and to analyze its characteristics of molecular epidemiology in Wuhan area. The newborn α-thalassemia gene in 1376 cases with positive confirmed in the primary screening in Wuhan area was detected by PCR, flow cytometry and FISH. The α-thalassemia in 436 newborns and α- β-composite thalassemia in 10 newborns were confirmed by detection in Wuhan area. The majority of thalassemia cases [up to 92.20% (402/436)] were found to be minor and static type thalassemia including 237 cases of -SEAαα (54.36%), 135 cases of -α3.7 / αα (30.96%) and 30 case of -α4.2/αα (6.88%), however, the intermediate type -α3.7/-SEA was found in 1 newborn. The -SEA/detetion, -α3.7/detetion and -α4.2/detetion were major in the detetion, the frequency was 54.12%, 32.29% and 7.13%, respectively; while the αCS mutation, αQS mutation and αWS mutation were less in the mutation, their frequency was 3.7%, 2.45% and 0.22% respectively. The minor and static type newborn thalassemia is most common, the incidence of detetion type -SEA/αα, -α3.7/αα and α4.2/αα is more high in Wuhan area of china.

Hematological and Molecular Characterization of a Novel Hb A2 Variant with Homozygous α-Thalassemia-2 in a Southern Thai Individual

We report here the hematological and molecular features of a novel δ-globin chain variant found in a Southern Thai woman. Her complete blood count was as follows: red blood cell (RBC) count 5.90 × 1012/L, hemoglobin concentration (Hb) 12.6 g/dL, packed cell volume (PCV) 0.41 L/L, mean corpuscular volume (MCV) 69.5 fL, mean corpuscular Hb (MCH) 21.4 pg, mean corpuscular Hb concentration (MCHC) 30.7 g/dL and RBC distribution width (RDW) 13.1%. The blood smear demonstrated microcytic hypochromic RBCs suggestive of thalassemia trait. Hemoglobin analysis identified Hb A2 + Hb A2-Kiriwong (2.4%) and Hb F (0.1%) on high performance liquid chromatography (HPLC). To characterize the α-thalassemia (α-thal) genotype, common α-thal-1 and α-thal-2 alleles were characterized by multiplex gap-polymerase chain reaction (gap-PCR). The results revealed homozygous α-thal-2 (–α3.7/–α3.7) in this case. DNA sequencing showed the presence of a novel δ-globin gene mutation [δ77(EF1)His→Arg; HBD: c.233A>G] that we named Hb A2-Kiriwong for the village from where the proband lived. In summary, the presence of microcytic hypochromic RBCs in this case was likely the result of the homozygous –α3.7 (rightward) deletion and was not affected by this Hb A2 variant.

Design, Validation, and Clinical Implementation of a Gap-Polymerase Chain Reaction Method for α-Thalassemia Genotyping Using Capillary Electrophoresis

α-Thalassemia (α-thal) is genetically heterogeneous with most cases caused by variably sized deletions of the HBA1 and/or HBA2 loci. In this report, we describe the development, validation, and implementation of a novel gap-polymerase chain reaction (gap-PCR)/capillary electrophoresis (CE). method. This assay utilizes two multiplex reactions and CE to detect the following deletions: –α3.7 (rightward), –α4.2 (leftward), –(α)20.5, – –SEA (Southeast Asian), – –MED, – –FIL and – –THAI. Validation studies using 36 previously characterized patient samples and plasmid controls demonstrated 100.0% accuracy. Following clinical implementation, 423 patients were analyzed over 24 months. Two hundred and twenty-seven cases (46.0%) showed abnormal results including heterozygous –α3.7 (n = 114, 27.0%), homozygous –α3.7 (n = 96, 23.0%), heterozygous – –SEA (n = 9, 2.0%), heterozygous –α 4.2 (n = 5, 1.0%), heterozygous – –MED (n = 1, <1.0%), and compound heterozygous –α3.7/–α4.2 (n = 2, <1.0%) deletions. Correlation with red blood cell (RBC) parameters showed that patients with a deletion of two or more genes were associated with significantly lower mean corpuscular volume (MCV) and mean corpuscular hemoglobin (Hb) (MCH) levels than patients with wild-type results. This novel multiplex gap-PCR protocol reliably detects the seven most common deletions giving rise to α-thal. Use of the fluorescently labeled CE method provides for a high throughput workflow suitable to a clinical diagnostic laboratory serving a multiethnic population.

The epidemiologic transition of thalassemia and associated hemoglobinopathies in southern Taiwan.

Since 1993, following the National Thalassemia Major Prevention Program and an increase in immigration and interracial marriages, especially in southern Taiwan, the distribution of hemoglobinopathies may have changed. This study investigates the epidemiologic transition of hemoglobinopathies. We analyzed 1870 specimens collected between 2003 and 2012 in southern Taiwan, used gap-polymerase chain reaction and PCR-restriction fragment length polymorphism-based methods, and confirmed genotypes of hemoglobinopathies by DNA sequencing. We found a 91% reduction in the incidence of thalassemia major compared with samples from between 1986 and 1995. The most common genotypes of α-thalassemia and α Hb variants were the SEA type (69.4%) and Hb Quong Sze (1.54%). The most common genotypes of β-thalassemia and β Hb variants were IVS-II-654 (46.2%) and Hb E (2.2%), respectively. Compared with studies performed in different areas of and time intervals in Taiwan, a higher prevalence of -α3.7, Hb Quong Sze, and Hb E and a lower prevalence of the SEA type were found in this study. However, the SEA type remained the most common genotype observed. In addition, an increasing number of cases with an -α3.7 type carrier, Hb Quong Sze carrier, and Gγ(Aγδβ)° were identified following a peak of interracial marriages between 2003 and 2005, reflecting a regional difference and the impact of interracial marriage. In conclusion, global migration and international marriage have changed the distribution of hemoglobinopathies in Taiwan. A more comprehensive prenatal screening for new immigrants with a longer follow-up is warranted.

Rapid diagnosis of common deletional α-thalassemia in the Chinese population by qPCR based on identical primer homologous fragments

ObjectiveIn China, −SEA, −α3.7 and −α4.2 are common deletional α-thalassemia alleles. Gap-PCR is the currently used detection method for these alleles, whose disadvantages include time-consuming procedure and increased potential for PCR product contamination. Therefore, this detection method needs to be improved. Based on identical-primer homologous fragments, a qPCR system was developed for deletional α-thalassemia genotyping, which was composed of a group of quantitatively-related primers and their corresponding probes plus two groups of qualitatively-related primers and their corresponding probes. In order to verify the accuracy of the qPCR system, known genotype samples and random samples are employed. ResultThe standard curve result demonstrated that designed primers and probes all yielded good amplification efficiency. In the tests of known genotype samples and random samples, sample detection results were consistent with verification results. ConclusionsIn detecting αα, −SEA, −α3.7 and −α4.2 alleles, deletional α-thalassemia alleles are accurately detected by this method. In addition, this method is provided with a wider detection range, greater speed and reduced PCR product contamination risk when compared with current common gap-PCR detection reagents.

Analysis of α1 and α2 globin genes among patients with hemoglobin Adana in Malaysia.

Hemoglobin (Hb) Adana [HBA2: c179G>A (or HBA1); p.Gly60Asp] is a non-deletional α-thalassemia variant found in Malaysia. An improvement in the molecular techniques in recent years has made identification of Hb Adana much easier. For this study, a total of 26 Hb Adana α-thalassemia intermedia and 10 Hb Adana trait blood samples were collected from patients. Common deletional and non-deletional α-thalassemia genotypes were determined using multiplex gap polymerase chain reaction (PCR) and multiplex ARMS PCR techniques. Identification of the Hb Adana location on the α-globin gene was carried out using genomic sequencing and the location of the mutation was confirmed via restriction fragment length polymorphism-PCR. Among the 36 samples, 24 (66.7%) had the -α(3.7)/α(Cd59)α mutation, while the -α(3.7)/α(Cd59)α mutation accounted for 2 samples (5.6%) and the remaining 10 (27.8%) samples were α/α(Cd59)α. All 36 samples were found to have the Hb Adana mutation on the α2-globin gene. The position of the α-globin gene mutation found in our cases was similar to that reported in Indonesia (16%) but not to that in Turkey (0.6%). Our results showed that the Hb Adana mutation was preferentially present in the α2-globin genes in Malays compared to the other ethnicities in Malaysia. Thus, the Malays might have similar ancestry based on the similarities in the Hb Adana position.

Neonatal screening for α‐thalassemia by cord hemoglobin Barts: how effective is it?

It has long been recognized that the hemoglobin (Hb) Bart's in cord blood is an accurate indicator of α-thalassemia and that the level of Hb Bart's was increased accordingly with the increasing numbers of the defective α-genes. This study used an automatic capillary electrophoresis system to determine the Hb Bart's levels in cord blood. Molecular analyses were used to detect various genotypes of α-thalassemia. Sixty-nine of the total 1169 newborns were found to have an increased Hb Bart's in cord blood, in whom the diagnosis of α-thalassemia was confirmed by the DNA analysis. The remaining 1100 newborns had no detectable Hb Bart's at birth; among these, 45 carriers of silent α-thalassemia were diagnosed by DNA analysis. All the 45 cases had only the -α(3.7) deletion genotype. For newborns of one α-gene mutation, especially for 3.7-kb deletion, the method based on Hb Bart's is inadequate and is therefore not reliable for screening.

Coinheritance of sickle cell anemia and α‐thalassemia delays disease onset and could improve survival in cameroonian's patients (Sub‐Saharan Africa)

Coinheritance of sickle cell anemia and α‐thalassemia delays disease onset and could improve survival in cameroonian's patients (Sub‐Saharan Africa)

Influence of the βs haplotype and α-thalassemia on stroke development in a Brazilian population with sickle cell anaemia

Stroke is a catastrophic complication of sickle cell anaemia (SCA) and is one of the leading causes of death in both adults and children with SCA. Evidence suggests that some genetic polymorphisms could be related to stroke development, but their association remains controversial. Here, we performed genotyping of five published single nucleotide polymorphisms, the α-thalassemia genotype, the G6PD A (-) variant deficiency, and the β(S) haplotype in a large series of SCA patients with well-defined stroke phenotypes. Of 261 unrelated SCA patients included in the study, 67 (9.5%) presented a documented, primary stroke event. Markers of haemolysis (red blood cell (RBC) counts, p = 0.023; reticulocyte counts, p = 0.003; haemoglobin (Hb) levels, p < 0.001; indirect bilirubin levels, p = 0.006; lactate dehydrogenase (LDH) levels, p = 0.001) were associated with stroke susceptibility. Genetically, only the β(S) haplotype (odds ratio (OR) 2.9, 95% confidence interval (CI) 1.56 to 4.31; p = 0.003) and the α(3.7kb)-thalassemia genotype (OR 0.31, 95% CI 0.11 to 0. 83; p = 0.02) were associated with increased and decreased stroke risk, respectively. In multivariate analysis, the β(S) haplotype was independently associated with stroke development (OR 2.26, 95% CI 1.16 to 4.4; p = 0.016). Our findings suggest that only the β(S) haplotypes and the α(3.7kb)-thalassemia genotype modulate the prevalence of stroke in our SCA population. Genetic heterogeneity among different populations may account for the irreproducibility amongst different studies.