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Immigration impact on genetic epidemiology of thalassemia worldwide is well-recognized. Over the past decade, the Duhok Province of Northern Iraq attracted a large number of immigrants. To assess whether immigration had contributed to changes in the mutation spectrum of β-thalassemia (β-thal) in the region, we recruited 218 registered patients with symptomatic β-thal. The recruited patients included 50 (22.9%) from resettled migrant families. A total of 431 β-thal alleles were fully characterized, with 20 different thalassemia mutations, the most frequent being IVS-II-1 (G>A) ( HBB : c.315 + 1G>A), IVS-I-6 (T>C) ( HBB : c.92 + 6T>C), codon 5 (-CT) ( HBB : c.17_18delCT), IVS-I-110 (G>A) ( HBB : c.93-21G>A), codon 44 (-C) ( HBB : c.135delC), codon 8 (-AA) ( HBB : c.25_26delAA) and IVS-I-1 (G>A) ( HBB : c.92 + 1G>A) constituting 72.8% of the total. Some differences in mutation spectrum were observed compared to earlier studies from this same province, the most notable of which were the higher frequencies of IVS-I-110 and codon 8. Interestingly, the highest proportions of alleles related to immigrants were encountered in these two allele groups. Ethnic variation was also documented, so that while Muslim Kurds had IVS-II-1, IVS-I-6, IVS-I-110, codon 5 and codon 44 as their most frequent mutations, the most frequent among Kurdish Yazidis, were codon 5, codon 44, codon 8 and IVS-I-6. These ethnic variations and changes in mutation spectrums are important and should be taken in consideration to ensure effective implementation of the thalassemia preventive program.

We report a novel frameshift β-thalassemia (β-thal) mutation due to a two-nucleotide deletion at codon 118 of the β-globin gene ( HBB : c.356_357delTT) in a 4-year-old Iraqi Kurd female presenting as transfusion-dependent β-thal. This frameshift mutation, unlike many others involving the third exon, behaved as a recessive β 0 defect and not as dominant β-thal mutation.

Multiple molecular tests are currently needed for accurate carrier testing for thalassemia. Therefore, long-molecule sequencing (LMS) was evaluated as an alternate on the PacBio Sequel platform for genotyping carriers of α-thalassemia or β-thalassemia. Multiplex long PCR was used to generate representative amplicons for the α (HBA1/2) and β (HBB) gene loci. Following LMS, circular consensus sequencing reads were aligned to the hg19 reference genome and variants called using FreeBayes software version 1.2.0. In a blinded study of 64 known carrier samples, all HBA1/2 and HBB variants detected by LMS were concordant with those independently assigned by targeted PCR assays. For HBA1/2 carrier samples, LMS accurately detected the common South East Asian, -α3.7, and -α4.2 deletions and four different rare single-nucleotide variants (SNVs). For HBB carrier samples, LMS accurately detected the most common Chinese insertion and deletion variant c.126_129delCTTT and 14 different SNVs/insertions and deletions and could discriminate compound heterozygous SNVs (trans configuration) and identify variants linked to benign SNPs (cis configuration). Overall, LMS displayed the hallmarks of a scalable, accurate, and cost-effective genotyping method. With further test coverage to additionally include detection of other clinically significant HBA1/2 copy number variations, such as the Thai, Mediterranean, and Filipino deletions, LMS may eventually serve as a comprehensive method for large-scale thalassemia carrier screening., (Copyright © 2020 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Consanguineous marriages potentially play an important role in the transmission of β-thalassaemia in many communities. This study aimed to determine the rate and socio-demographic associations of consanguineous marriages and to assess the influence on the prevalence of β-thalassaemia in Sri Lanka. Three marriage registrars from each district of Sri Lanka were randomly selected to prospectively collect data on all couples who registered their marriage during a 6-month period starting 1st July 2009. Separately, the parents of patients with β-thalassaemia were interviewed to identify consanguinity. A total of 5255 marriages were recorded from 22 districts. The average age at marriage was 27.3 (±6.1) years for males and 24.1 (±5.7) years for females. A majority (71%) of marriages were 'love' marriages, except in the Moor community where 84% were 'arranged' marriages. Overall, the national consanguinity rate was 7.4%. It was significantly higher among ethnic Tamils (22.4%) compared with Sinhalese (3.8%) and Moors (3.2%) (p < 0.001). Consanguinity rates were also higher in 'arranged' as opposed to 'love' marriages (11.7% vs 5.6%, p < 0.001). In patients with β-thalassaemia, the overall consanguinity rate was 14.5%; it was highest among Tamils (44%) and lowest among Sinhalese (12%). Parental consanguinity among patients with β-thalassaemia was double the national average. Although consanguinity is not the major factor in the transmission of the disease in the country, emphasis should be given to this significant practice when conducting β-thalassaemia prevention and awareness campaigns, especially in high-prevalence communities.

Objective: The aim of the study was to explore genotype distribution thalassemia and G6PD deficiency in Meizhou city, China., Methods: A total of 16 158 individuals were involved in thalassemia genetic testing. A total of 605 subjects were screened for common Chinese G6PD mutations by gene chip analysis. Genotypes and allele frequencies were analyzed., Results: A total of 5463 cases carried thalassemia mutations were identified, including 3585 cases, 1701 cases, and 177 cases with α-, β-, and α + β-thalassemia mutations, respectively. -- SEA (65.12%), -α 3.7 (19.05%), and -α 4.2 (8.05%) deletion were the main mutations of α-thalassemia, while IVS-II-654(C → T) (40.39%), CD41-42(-TCTT) (32.72%), -28(A → G) (10.11%), and CD17(A → T) (9.32%) mutations were the principal mutations of β-thalassemia in Meizhou. There were significant differences in allele frequencies in some counties. Genetic testing for G6PD deficiency, six mutation sites, and one polymorphism were detected in our study. A total of 198 alleles with the mutation were detected among 805 alleles (24.6%). G6PD Canton (c.1376 G → T) (45.96%), G6PD Kaiping (c.1388 G → A) (39.39%), and G6PD Gaohe (c.95 A → G) (9.09%) account for 94.44% mutations, followed by G6PD Chinese-5 (c.1024 C → T) (4.04%), G6PD Viangchan (c.871G → A) (1.01%), and G6PD Maewo (c.1360 C → T) (0.51%). There were some differences of the distribution of G6PD mutations among eight counties in Meizhou., Conclusions: The -- SEA , -α 3.7 , and -α 4.2 deletion were the main mutations of α-thalassemia, while IVS-II-654(C → T), CD41-42(-TCTT), -28(A → G), and CD17(A → T) mutations were the principal mutations of β-thalassemia in Meizhou. G6PD c.1376 G → T, c.1388 G → A, and c.95 A → G were the main mutations of G6PD deficiency. There were some differences of the distribution of thalassemia and G6PD mutations among eight counties in Meizhou., (© 2019 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals, Inc.)

The present study was intended to report the incidence of the most frequently occurring β-thalassemia (β-thal) mutations in the Kohat region [Khyber Pakhtunkhwa (KP) Province, Pakistan], their inheritance pattern in patients, and consanguinity in the parents. Moreover, this study could provide valuable information regarding thalassemia diagnoses such as prenatal diagnosis (PND), genetic counseling and carrier screening for controlling the affected births in the population. During this study, 160 peripheral blood samples of affected patients, their parents and siblings were collected from 25 discrete families having at least one child needing regular blood transfusions from different areas of the Kohat region. β-Thalassemia mutations found in the population were screened via the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). A total of 320 alleles was evaluated for the presence of six β-thal mutations. Of these six β-thal mutations, the frameshift codons (FSC) 8/9 (+G) ( HBB : c.27&#95;28insG) was found to be the most frequent in the studied population, and more interestingly, followed by IVS-I-5 (G>C) ( HBB : c.92+5G>C) and FSC 5 (-CT) ( HBB : c.17&#95;18delCT). The findings of the present study show differences with previous results from other regions of the Pashtun population, which demarcates the heterogeneity in mutations found in the Pashtun ethnicity. These observations may help in implementing parental meetings about disease recurrence in future, large scale mutation screening and PND for the population of the Kohat region and also the whole Pashtun ethnicity.

β-Thalassemia (β-thal) is one of the most common inherited hemoglobin (Hb) disorders in southern China. Up to now, the mutation spectrum of β-thal has been increasingly broadened through various molecular methods. In this study, a 34-year-old female displaying microcytic, hypochromic anemia was first detected with a novel IVS-I-6 (T>G) ( HBB : c.92+6T>G) mutation by Sanger sequencing. Pedigree analysis performed on her family showed that her mother and her daughter, who had abnormal hematological indices, also carried this mutation, while her other family members with normal hematological phenotypes, were not detected to carry any mutation. Based on the observed symptoms in this Chinese family, we concluded that this novel mutation was associated with a mild β-thal phenotype.

The best approach for prevention of alloimmunization in β-thalassemia (β-thal) patients is perfect matching of all red blood cell (RBC) antigens associated with clinically significant antibodies, but this is expensive and may limit the blood supply. Knowing the most common alloantibodies in transfusion-dependent β-thal patients make it possible to establish more cost-effective matching strategies for high-risk antigens. With this in mind, we intended to determine the most common alloantibodies in different parts of Iran. A total of 480 alloimmunized β-thal major (β-TM) patients who were referred to the Tehran Adult Thalassemia Clinic in Tehran, Iran from all provinces between 2015 and 2017, were included in this study. Antibody screening was performed on the fresh serum of all patients. Subsequently, the specification of antibodies was identified using a panel of recognized blood group antigens. Anti-K was the most common alloantibody detected in β-TM patients in all regions of Iran. The prevalence of this antibody reached to 37.7% in the western area, but in southeastern region, anti-E was predominant. Interestingly, the rare alloantibody anti-Kp a was detected with a high prevalence in the western region. The antibodies against E and D antigens were also encountered with high prevalence in most regions of the country. The present study demonstrated the distribution of alloantibodies in alloimmunized transfusion-dependent β-thal patients from diverse ethnic and racial backgrounds of the Iranian population. The results of this study can be used as a basis to establish cost-effective RBC phenotyping and matching strategies for high-risk antigens in donors and chronic transfusion recipients in different regions of Iran.

Patients with unstable hemoglobin (Hb), caused by a qualitative abnormality in α- and β-globin genes, are often asymptomatic or mildly symptomatic. It is often difficult to diagnose unstable Hb patients with only mild hemolysis or low oxygen saturation. We herein report a case of a family with an unstable Hb, specifically, Hb Sydney ( HBB : c.203T>C), an abnormal β-globin chain. A 5-year-old boy was referred to our hospital for low percutaneous oxygen saturation (SpO 2 ) in the setting of bronchitis. During hospitalization, low SpO 2 persisted despite the improvement in respiratory distress symptoms. As he had mild hemolysis and splenomegaly, his disease was diagnosed to carry Hb Sydney based on gene analysis. His mother and brother also carried Hb Sydney. In this case, bronchial asthma had been treated, but unstable Hb was not assessed. Low SpO 2 may be tolerated and overlooked in cases of asthma and it took time to diagnose this patient. The present case suggests that unstable Hb should be considered in patients with bronchial asthma and prolonged low SpO 2 .

This study assessed thalassemia and hemoglobinopathies in a group of the Tay ethnic minority. Participants included 289 women of reproductive-age who enrolled in a pilot screening program for thalassemia conducted at six communities of Thai Nguyen Province, northern Vietnam. Standard procedures including complete blood count (CBC), hemoglobin (Hb) and DNA analyses were performed for all samples. The prevalence of thalassemia in 289 Tay women was 15.6% (gene frequency 0.078) for α 0 -thalassemia (α 0 -thal), 10.0% (gene frequency 0.050) for α + -thal, 7.3% (gene frequency 0.036) for β-thalassemia (β-thal), 2.4% (gene frequency 0.012) for Hb Constant Spring [Hb CS; α142, Term→Gln, T AA> C AA (α2), HBA2 : c.427T>C] and 1.7% (gene frequency 0.009) for Hb E [β26(B8)Glu→Lys, G AG> A AG; HBB : c.79G>A]. Further analysis of β-globin gene abnormalities identified four mutations including codons 41/42 (-TCTT) ( HBB : c.126&#95;129delCTTT), codon 17 (A>T) ( HBB : c.52A>T), codons 71/72 (+A) ( HBB : c.216&#95;217insA), and -28 (A>G) ( HBB : c.78A>G). The results hint at the remarkably high frequencies of severe forms of thalassemia that indicate a serious public health problem requiring further exploration, and most probably, also intervention within the country.

This prospective study assessed the prevalence and genetic analysis of α - and β -thalassemia and sickle cell anemia (SCA) in Southwest Iran. Hematological indices were measured in 17,581 couples living in Khuzestan Province, Southwest Iran. Individuals with mean corpuscular volume <80, mean corpuscular hemoglobin <27, hemoglobin A2 ≥3/5 were considered as β -thalassemia traits. Prevalence of minor β -thalassemia, α -thalassemia, SCA, iron deficiency anemia, and silent thalassemia were respectively identified in 995 (5.6%), 1169 (6.65%), 1240 (7.05%), 911 (5.18%), and 1134 (6.45%) individuals using a multiplex amplification refractory mutation system, and direct DNA sequencing of globin genes. Three codons IVS-II-1 (G → A; 26%; n = 13), IVS-I-1 (G → T; 16%; n = 8), and IVS-I-110 (G → A; 14%; n = 7) were the most frequent mutants and IVS-II-1 was the most common β -thalassemia mutation. Also, based on a gap-polymerase chain reaction assay, genotype frequencies of α -globin mutations were - α 3.7 kb (50%; n = 25), Med/ αα thal (12%; n = 6), and - α 4.2/ αα (10%; n = 5), which were the most frequent deletion mutants (72% in total). The most common deletion (50%) was - α 3.7 kb . Our data suggest that the population of Southwest Iran is at high risk of α - and β -thalassemia caused by these deletion mutants and SCA. Our findings will be useful for developing an efficient control program and genetic counseling., Competing Interests: Dr. Forozan H. Nezhad, First author, has received research grants from Ahvaz Jundishapur University of Medical Sciences. Other co-authors report no conflicts of interest relevant to this article., (© Atlantis Press International B.V.)

Hemoglobinopathies and thalassemias are the most commonly encountered monogenic disorders of blood in humans, posing a major genetic and public health problem round the globe. Hb S (HBB: c.20A>T)-β-thalassemia (β-thal) is a compound aberrant heterozygosity with inconsistent phenotypic expression, which are poorly described and clinically mapped. Comprehensive genetic characterization of such a population is highly warranted for complete understanding of the clinical heterogeneity, disease prognosis and therapeutic management. In this study, Hb S-β-thal (n = 60) patients, strictly defined by varying degrees of clinical presentations, were selected to evaluate their genotype-phenotype agreement. Furthermore, β-globin (n = 120) and α-globin gene clusters (n = 60) were genetically characterized and statistically correlated with clinical terminologies to explain the clinical heterogeneity. Our results revealed the association of the Arab-Indian haplotypes with nine different frameworks of β-thal together with the modulating role of α-thalassemia (α-thal). The study subjects, including carriers of β-thal haplotype III [- - - - - - -] (8.0%), presented with varying severe patterns of clinical symptoms such as painful crisis, multiple infections and splenomegaly, as an outcome of significantly less Hb F and higher Hb S levels (p < 0.5). The study findings indicated that together with α-thal, β-thal haplotypes and Hb F levels, may possibly provide a close justification to support the clinical heterogeneity in the study population.

Thalassemia is one of the most common hereditary blood disorders. Epidemiological data regarding the occurrence and distribution of thalassemia is important for designing appropriate prevention strategies. The objective of this study was to update and reveal the prevalence of thalassemia and mutation spectrum in the Baise region of southern China. We screened 47,500 individuals from Baise region by hematological and genetic analysis. Totally, 11,432 (24.07%) subjects were diagnosed as being carriers and patients of thalassemia, including 7290 (15.35%) subjects with α-thalassemia, 3152 (6.64%) subjects with β-thalassemia and 990 (2.08%) subjects with both α-thalassemia and β-thalassemia. Ten α-thalassemia mutations and 31 genotypes were identified in the α-thalassemia carriers and patients. Meanwhile, 13 β-thalassemia mutations and 26 genotypes were characterized in the β-thalassemia carriers and patients. Furthermore, the true prevalence of nondeletional mutations and Thailand type (-THAI) deletion mutation were first reported in this study. In addition, three cases of αα/ααα3.7, five cases of HKαα/αα and two rare β-globin mutations, -86 (G>C) and CD 121 (G>T) were first identified in the Chinese Zhuang ethnic populations. Our data indicated that there was great heterogeneity and extensive spectrum of thalassemias in the Baise populations. The findings will be useful for genetic counseling and prevention of severe thalassemia in this region., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objectives: To characterize and quantitate hemoglobin (Hb) variants discovered during biometric hemoglobin A1c (HbA1c) analyses in a large multiethnic population with a focus on the effect of variants on testing method and results., Methods: In total, 13,913 individuals had their HbA1c measured via ion-exchange high-performance liquid chromatography. Samples that had a variant Hb detected or HbF fraction more than 25% underwent variant Hb characterization and confirmation by gel electrophoresis. RBC indices were also evaluated for possible concomitant thalassemia., Results: Of the 13,913 individuals evaluated, 524 (3.77%) had an Hb variant. The prevalence of each variant was as follows: HbS trait (n = 396, 2.85%), HbSS disease (n = 4, 0.03%), HbC trait (n = 85, 0.61%), HbCC disease (n = 2, 0.01%), HbSC disease (n = 5, 0.04%), HbE trait (n = 18, 0.13%), HbD or G trait (n = 9, 0.06%), HbS β-thalassemia + disease (n = 1, 0.01%), hereditary persistence of HbF (n = 2, 0.01%), and HbMontgomery trait (n = 1, 0.01%). Concomitant α-thalassemia was detected in 20 (3.82%) of the 524 individuals with an Hb variant., Conclusions: This study represents one of the largest epidemiologic investigations into the prevalence of Hb variants in a North American metropolitan, multiethnic workforce and their dependents and reinforces the importance of method selection in populations with Hb variants., (© American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

The molecular basis of β-thalassemia (β-thal) mutations in North and in South Vietnam have been described during the past 15 years, whereas limited data were available concerning the central area of the country. In this study, we describe the molecular characterization and frequency of β-globin gene mutations in the Thua Thien Hue Province of Central Vietnam as the result of a first survey conducted in 22 transfusion-dependent patients, and four unrelated heterozygotes. Nine different known mutations were identified (seven of the β 0 and two of the β + type) in a total of 48 chromosomes. The most common was codon 26 (G>A) or Hb E (HBB: c.79 G>A) accounting for 29.2% of the total studied chromosomes, followed by codon 17 (A>T) (HBB: c.52 A>T) (25.0%), and codons 41/42 (-TTCT) (HBB: c.126&#95;129delCTTT) (18.8%). Other mutations with appreciable frequencies (6.3-8.3%) were IVS-I-1 (G>T) (HBB: c.92+1 G>T), codon 26 (G>T) (HBB: c.79 G>T) and codons 71/72 (+A) (HBB: c.216&#95;217insA). Relatively rarer (2.0%) were the promoter -28 (A>G) (HBB: c.78 A>G) mutation, the codon 95 (+A) (HBB: c.287&#95;288insA), which is reported only in the Vietnamese, and the codons 14/15 (+G) (HBB: c.45&#95;46insG) mutation, thus far observed only in Thailand. Results are relevant for implementing appropriate measures for β-thal prevention and control in the region as well as in the whole country.

Thalassaemia is the most common monogenic disorder worldwide. It is common in areas with prevalent malaria as thalassaemic red cells provide immunity against the parasite. The incidence of thalassaemia carriers is high in regions such as Mediterranean, Middle East, Indian subcontinent, Southeast Asia and South China. In the past few decades, migrants from the thalassaemia prevalent countries to non-prevalent countries, mainly North America and Central and North Europe, are rapidly increasing in number. The non-prevalent countries may not have established pre-natal screening system for thalassaemia. The genetic subtypes among the different ethnic groups vary; this may pose challenges in prenatal diagnosis. Genetic counselling on the postnatal course of thalassaemia may be affected by the genotype-phenotype correlation and coinheritance of other genetic diseases. New treatment methods improve the survival of patient with thalassaemia major, but some late complications that occur with longer survival have been recently discovered., (Copyright © 2016. Published by Elsevier Ltd.)

Objectives: β-Thalassaemia is widely found in Southwestern China. Characterisation of β-thalassaemia can improve screening and prenatal diagnosis for at-risk populations., Design: A retrospective study., Methods: In this study, the levels of haemoglobin alpha 2 (HbA 2 ) and haemoglobin alpha (HbA) were analysed by gender for a total of 15 067 subjects screened by capillary electrophoresis. The cut-off value with the highest accuracy was established to identify β-thalassaemia in 723 patients suspected to have this disease. Haematological and electrophoretic characterisation of eight common types of β-thalassaemia were analysed in 486 β-thalassaemia subjects., Results: HbA levels were significantly higher in men than in women, but there was no significant difference on HbA 2 levels. A new cut-off value for the diagnosis of β-thalassaemia (HbA 2 ≥4.0%) with the highest accuracy was proposed for the studied populations. Haemoglobin (Hb) was significantly higher in men compared with women (p<0.05), whereas no statistically significant differences were found for mean cell volume (MCV), mean cell haemoglobin (MCH), HbA and HbA 2 . The haemoglobin E (HbE) group showed comparatively higher values for haematological indices (Hb, MCV and MCH) than the other genotypes in heterozygous β-thalassaemia groups (p<0.05), and -28 (A>G) (HBB (β-globin):c.-78A>C) had significantly higher HbA 2 values compared with other β-thalassaemia., Conclusions: Ethnic groups have diversified β-globin gene mutations and considerable haematological variations. Our study will lay the foundation for screening programmes and clinical management of thalassaemia in Southwestern China., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objective: To analyze the genotype-phenotype correlation among carriers from Guangdong with co-inherited hemoglobin Hb Westmead (HbWS) and β-thalassemia., Methods: Twenty three patients (including 9 males and 14 females, aged 1-53 year old) were diagnosed by hematological analysis and genetic testing. Complete blood cell count and hemoglobin electrophoresis analysis were performed on a XE4000i automatic hemocyte analyzer. Hb, HbF and HbA2 were tested by high performance liquid chromatography (HPLC). Gap-PCR was adopted to detect three common thalassemia deletions. Reverse dot-blotting (RDB) assay was applied for detecting three common non-deletional α2 gene mutations and β-thalassemia., Results: Among the 23 patients, 12 showed anemia, among whom 9 had mild anemia and 3 had moderate anemia. The lowest Hb was 68 g/L, and both mean corpuscular volume and mean corpuscular hemoglobin were lower than average, while HbA2 was higher than 3.5%. Genetic analysis confirmed that 5 cases had αWS-α/α-α, β CD654/β N (21.7%), 4 had α WS-α/α-α, β CD41-42/β N (17.4%), 5 had α WS-α/α-α, β CD17/β N (21.7%), 4 had α WS-α/α-α, β CD28/β N (17.4%), 1 had α WS-α/α-α, β CD71-72/β N (4.3%), 1 had αWS-α/α-α, β CD27-28/β N (4.3%), 1 had α WS-α/α-α, β CD41-42/β CD17 (4.3%), 2 had a concomitant β-thalassemia heterozygosity and -α 3.7 deletion., Conclusion: Patients with co-existing Hb WS and other β-thalassemia trait may show variable clinical features. Such compound heterozygotes are usually misdiagnosed during screening by hemoglobin electrophoresis, accurate diagnose should be attained by molecular diagnosis.

Objective: To investigate the common mutation spectrum of α- and β-thalassemia in Yunnan childbearing-aged population., Methods: The common mutation types of α- or β-globin genes were detected by multiple Gap-PCR and the PCR-reversed dot blotting, and the unknown mutation types were determined by DNA sequencing in DNA samples of hypochromic microcytic anemia patients and carriers who were confirmed to be positive by serologic screaning, then the mutation types of globin in Yunnan population were analyzed statistically., Results: A total of 40 kinds of mutation types were detected in 685 detected persons, among them the 3 commonest mutation types of α-globin genes were --(SEA)/αα (49.09%), -α(3.7)/αα (36.67%) and α(CS)α/αα (8.79%), the 3 commonest genetypes of β-globin gene were CD26(GAG>AAG)/N (43.78%), CD41-42(-CTTT)/N (20.1%) and CD17(AAG>TAG)/N (18.9%). There were 348 Han and 212 Dai ethnic persons in 685 cases, but their mutation of globin genes were different between these 2 ethnic groups. The results also showed that the gene mutation types were mostly concentrated in Dai ethnic individuals, since 28 of 38 detected α-β-thalassemia cases were Dai ethnic individuals., Conclusion: The mutation spectrums of α- and β-globin genes in Yunnan childbearing-aged population are diverse and different from that in other areas of China.

Objective: To investigate the gene mutation spectrum of β-thalassemia in Dai ethnic population of 2 border region in Chinese Yunnan Province., Methods: The patients with β-thalassemia in Dai ethnic population of Dehong and Xishuangbanna autonamic prefecture were screened by using blood routine detection and capillary electrophoresis. The β-globin gene mutation in patients with β-thalassemia were detected by using PCR reverse dot-blot hybridization (PCR-RDB), the constitutive rate of gene mutation in patients with β-thalassemia of Dai ethnic population in two border regions was analyzed and compared., Results: A total of 186 patients with gene mutation of β-thalassemia were confirmed. Among them, 10 gene mutation were found, and the 5 main gene mutations were CD26 (62.56%), CD41-42 (18.97%), CD17 (14.36%), CD71-72 (2.05%) and IVS-II-654 (1.54%). Among Dai ethinic population in Dehong region, 4 gene mutations were found including CD26 (80.31%), CD17 (11.02%), CD41-42 (6.30%) and CD71-72 (2.36%). Among Dai ethinic population in Xishuangbanna region, 6 gene mutations were found, out of them the more common gene mutations were CD41-42 (42.64%), CD26 (29.41%) and CD17 (20.59%)., Conclusion: The gene mutations of β-thalassemia in Dai ethinic population of Yunnan province has been confirmed to be more genetic heterogenicity, the spectrums of β-thalassemia mutations in Dai ethinic population of different regions were significant different.

Objective: The aim of this study was to investigate the prevalence of hemoglobin E (Hb E) as well as the hematological and the phenotypic features of Hb E-related disorders in Yunnan Province of Southwest China., Methods: A total of 30,908 individuals from more than 30 nationalities who were childbearing population were recruited in the present study. Hematological analysis including complete blood counts and quantification of Hb levels were performed by capillary electrophoresis. The identified carriers were further detected for molecular analysis by multiple gap-polymerase chain reactions (gap-PCR) and the PCR-reverse dot-blot., Results: Hematological results showed that 345 subjects were identified to be Hb E carriers (1.1%). The high incidence of carrying Hb E occurred in Achang (25.0%), Jingpo (23.5%), Dai (16.0%), and Lisu (13.6%). After performing molecular analysis in 201 carriers, 192 cases (95.5%) were heterozygous Hb E and 29 cases (14.4%) of Hb E were con-inherited with α-thal cases. The other β-globin chain mutation included homozygous Hb E (three cases), β(+)-thal/Hb E (one case) and β(0)-thal/Hb E (five cases). Individuals in Dai had the most types of Hb E-related disorders. Severe anemia was observed in cases of β(+)-thal/Hb E and β(0)-thal/Hb E., Conclusions: There is a high prevalence of Hb E among Yunnan populations, especially in ethnic groups. In addition, the spectrums of Hb gene mutations would provide a support for the genetic counseling of Hb E-related disorders among Yunnan populations.

Objectives: This study aimed to detect α- and β-thalassaemia mutations in the Jino ethnic minority population of Yunnan Province, Southwest China., Design: A total of 1613 Jino adults were continuously recruited from February 2012 to April 2012. Fasting venous blood samples were obtained to determine haematological variables. Haemoglobin analysis was conducted using high-performance liquid chromatography. Participants with hypochromic microcytic anaemia or positive haemoglobin analysis profiles were confirmed by α- and β-globin genetic testing, including DNA microarray analysis, direct sequencing methods and multiplex gap-PCR assays., Setting: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital., Results: We found 363 suspected cases by primary screening of haematological variables and haemoglobin analysis. After further genetic testing, four types of α- and β-thalassaemia mutation were detected in 203 out of 363 individuals. Both α(0)- and α(+)-thalassaemia mutations, --(SEA) and -α(3.7), were identified. β-Thalassaemia mutations included CD17 (HBB:c.52A>T) and CD26 (HbE or HBB:c.79G>A). In addition, 13 HbE carriers had coexisting α(0)- or α(+)-thalassaemia deletions. Clinical haematological variables indicated that, in this study, carriers of all thalassaemic genotypes had more severe hypochromic microcytic anaemia than non-thalassaemic individuals., Conclusions: Our results provide information on the Jino ethnic minority that may be useful for further genetic counselling, prenatal screening and clinical diagnosis of thalassaemia in this region., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

This study investigated the prevalence of iron-deficiency anaemia, glucose-6-phosphate dehydrogenase (G6PD) deficiency and β-thalassaemia trait among Arab migrating nomad children in southern Islamic Republic of Iran. Blood samples were analysed from 134 schoolchildren aged < 18 years (51 males, 83 females). Low serum ferritin (< 12 ng/dL) was present in 17.9% of children (21.7% in females and 11.8% in males). Low haemoglobin (Hb) correlated significantly with a low serum ferritin. Only 1 child had G6PD deficiency. A total of 9.7% of children had HbA2 ≥ 3.5 g/dL, indicating β-thalassaemia trait (10.8% in females and 7.8% in males). Mean serum iron, serum ferritin and total iron binding capacity were similar in males and females. Serum ferritin index was as accurate as Hb index in the diagnosis of iron-deficiency anaemia. A high prevalence of β-thalassaemia trait was the major potential risk factor in this population.

Background: The "gray zone" of borderline hemoglobin A2 (Hb A2) may be present in a large section of the population, especially in countries where thalassemia is common. However, very little is currently known of the molecular basis of borderline Hb A2 in Chinese individuals., Method: In this study, we performed a comprehensive analysis of the globin genotypes and KLF1 gene mutations associated with borderline Hb A2 in 165 Chinese subjects., Result: Fifteen (9.1%) were positive for a molecular defect in the α-,β-globin genes, of whom, α-thalassemia mutations and α-globin gene triplication were found in eleven cases, accounting for about 73.3% of these globin gene defects. Twenty (12.1%) were positive for a molecular defect in the KLF1 gene. Eight different mutations were identified, six of which are here reported for the first time. The most common is the G176AfsX179 mutation, accounting for 50% of the total., Conclusions: The molecular characterization of borderline Hb A2 in Chinese individuals is significantly different than in Italian population. Our data is conductive to provision of genetic counseling for Chinese individuals with borderline Hb A2., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To investigate the spectrum of β -thalassemia mutations in Guizhou Province., Methods: For 542 individuals suspected to have β -thalassemia by decreased mean corpuscular volume (MCV) and corpuscle hemoglobin (MCH) by routine blood test and hemoglobin electrophoresis, reverse dot blot hybridization (RDB) was performed to detect 17 known β -thalassemia mutations, including 8 common and 9 rare mutations. For cases where no mutation was identified, the entire human β -globin gene was screened to find other rare mutations. The distribution and frequencies of detected β -thalassemia mutations were then analyzed., Results: A total of 460 individuals were diagnosed as β -thalassemia by DNA analysis, which included 352 heterozygotes, 67 compound heterozygotes and 41 mutant homozygotes. A total of 12 β -thalassemia mutations were detected in these individuals. The mutations have ranked from high to low frequency as: CD17 (40.74%), CD41-42 (33.69%), IVS-II-654 (13.76%), -28 (3.70%), β E (3.35%), CD71-72(1.94%), CD43 (1.06%), IVS-I-1 (0.71%), CD27-28 (0.35%), -29(0.35%), CAP (0.18%), and CD121 (0.18%). The former six mutations have accounted for 97.18% of all. CD121 (GAA> TAA) detected from a heterozygote, as a dominant mutation, has been firstly found in the Chinese population., Conclusion: The spectrum of β -thalassemia in Guizhou Province showed certain distinct characteristics, with CD17 being the most common mutation. The newly discovered mutation of CD121 has expanded the spectrum of β -thalassemia in Chinese population. Our result may provide valuable information for the prevention and control of β -thalassemia in Guizhou.

The main hereditary hemoglobin (Hb) disorder in Argentina is β-thalassemia (β-thal). Molecular studies performed in the center of the country exhibited a marked prevalence of the codon 39 (C > T) and IVS-I-110 (G > A) mutations. The northwest region of Argentina has a different demographic history characterized by an important Spanish influx. Seventy-one β-thal carriers attending the Instituto de Bioquímica Aplicada, Tucumán, Argentina, were investigated for β-globin gene mutations by real-time polymerase chain reaction (RT-PCR). To examine the genotype-phenotype relationship, mean corpuscular volume (MCV), mean corpuscular Hb (MCH) and Hb A2 were measured. In order to recognize β-thal, Mentzer Index, Shine & Lal and Red Cell Distribution Width Index (RDWI), were calculated. The ethnic background of subjects revealed that 82.0% of the population was of Italian, Spanish and Arab origin. Seven mutations were detected: codon 39 (45.0%), IVS-I-1 (G > A) (22.5%), IVS-I-110 (16.3%), IVS-II-1 (G > A) (4.1%), IVS-I-1 (G > T) (2.0%), IVS-I-6 (T > C) (2.0%) and IVS-II-745 (G > C) (2.0%). In three families (6.1%), β-thal mutations were not determined. These results differed from other Argentinian studies because at present codon 39 and IVS-I-1 are the most prevalent; MCV, MCH and Hb A2 did not correlate with the type of mutation (β(0)/β(+)). Values of MCV (67.0 fL) and Hb A2 (4.85%) were unable to discriminate between them. Significant differences (p < 0.05) in MCV, MCH and Shine & Lal were observed between the undetermined group and the three most common mutations. These data show different patterns of β-thal mutations in the center and northwest regions of Argentina. Differences might represent the influence of Spanish immigration.

Different thalassemia mutations have been reported in various ethnic groups and geographical regions in India. In this study, we have investigated Kachhiya Patel, Dhodia Patel, Modh Bania, and Muslim communities of Surat, Gujarat to identify molecular defects causing β-thalassemia in them. Covalent reverse dot blot hybridization technique was used to detect six common Indian β-thalassemia mutations while the seventh mutation (619-bp deletion) was identified by PCR. The less common mutations were detected by amplification refractory mutation and the uncharacterized samples were directly sequenced. Characterization of β-thalassemia mutations was carried out in a total of 175 unrelated β-thalassemia trait cases. We identified IVS 1 nt 5 (G → C) in 31 out of 65 Muslims, codon (Cd) 41/42 (-CTTT) in 14 out of 16 in Modh Banias, Cd 15 (G → A) in 19 out of 24 Dhodia Patels. The most significant observation was an uncommon mutation; Cd 30 (G → A) detected in 61 out of 70 Kachhiya Patels. The 619-bp deletion was detected in 6 out of 10 Muslim-Memons. Many other rare mutations like Cd 15 (-T), Cd 8 (-AA), -88 (C → A), Capsite +1 (A → C), Cd 16(-C), and Cd 5 (-CT) were detected. To our knowledge, our study is the first to characterize β-thalassemia mutations in the Kachhiya Patel community. This study will facilitate molecular analysis and prenatal diagnosis in these four communities.

There is a need for higly accurate non-invasive methods for assessing organ iron content in thalassaemia patients. This study evaluated the relation between serum ferritin level, liver enzyme levels and hepatitis C antibody and liver and heart iron deposition assessed by MRI T2*. Data were obtained from the medical records of 156 thalassemia major patients in Tehran. There was a moderate negative correlation between serum ferritin and liver MRI T2* relaxation time (r = -0.535) and a weak negative correlation between serum ferritin and heart MRI T2* relaxation time (r = -0.361). Hepatitis C infection and liver enzyme levels did not confound or modify the relation between ferritin and liver or heart MRI T2*. Liver and heart MRI T2* readings were poorly correlated (r = 0.281). Routine evaluation of liver and heart iron content using MRI T2* is suggested to better evaluate the haemosiderosis status in thalassemia patients.

Beta-thalassemia is a life-threatening inherited blood disorder. Rapid characterization of β-globin gene mutations is necessary because of the high frequency of Malaysian β-thalassemia carriers. A combination real-time polymerase chain reaction genotyping assay using TaqMan probes was developed to confirm β-globin gene mutations. In this study, primers and probes were designed to specifically identify 8 common β-thalassemia mutations in the Malaysian Malay and Chinese ethnic groups using the Primer Express software. "Blind tests" using DNA samples from healthy individuals and β-thalassemia patients with different genotypes were performed to determine the specificity and sensitivity of this newly designed assay. Our results showed 100% sensitivity and specificity for this novel assay. In conclusion, the TaqMan genotyping assay is a straightforward assay that allows detection of β-globin gene mutations in less than 40 min. The simplicity and reproducibility of the TaqMan genotyping assay permit its use in laboratories as a rapid and cost-effective diagnostic tool for confirmation of common β-thalassemia mutations in Malaysia.

Objective: To investigate the incidence and the gene mutation frequencies and patterns of β-thalassemia (β-Thal) in ethnic Han children in Chongqing city., Method: A total of 1726 children were screened by using automatic hemocytic analyzer, cellulose acetate electrophoresis and fetal hemoglobin alkali denaturation test. Samples with mean corpuscular volume (MCV) < 80 fl, cell hemoglobin content (MCH) < 27 pg and hemoglobin A2 (HbA2) levels >3.3%, fetal hemoglobin (HbF) >2% for β-Thal screening indicators. The positive samples of screening indicators were detected and identified by PCR-reverse dot blot method for 18 common β-Thal mutations in Chinese populations, unknown mutations samples were subjected to DNA sequencing analysis of the β-globin gene., Result: Twenty-five cases of β-Thal carriers were observed from the 1726 samples, with 24 cases of β-Thal heterozygote and one case of double heterozygote. Therefore, the β-Thal carrier rate was 1.51%. After 1726 peripheral venous blood samples analyzed by hematological parameters, 164 positive cases of β-Thal screening indicators were found, with the positive rate being 9.50% (164/1726). A total of 6 different gene mutations were detected, the four most common mutations were as the following: CD41-42, IVS-II-654, CD17 and beta E. These four mutations as the major types in this area accounted for 88.00% of all the mutations. In addition, one rare mutation of 5 'UTR; + (43 -40) was found, and one case of the hemoglobin variant of Hb Zurich was reported in Chinese people for the first time., Conclusion: Chongqing is a high risk region of the β-Thal. Epidemiological Data from the research was useul for the genetic counseling and the prevention of β-Thal major.

β-Thalassemias are an inherited group of disorders of hemoglobin (Hb) and comprise the most common monogenic disorders in Azerbaijan. They are extremely heterogeneous at the molecular level. Here we report the first identification of a patient who is a compound heterozygote for two rare β-thalassemia (β-thal) mutations, IVS-I-130 (G>C) and codon 37 (TGG>TGA).

Aim: Sickle-cell disease (SCD) is more prevalent in Australia due to increased migration; however, the Australian paediatric SCD population has not been previously described. This study aimed to identify the demographic features of and quantify the hospital resource utilisation in the SCD population at The Royal Children's Hospital in Victoria., Methods: This was a retrospective chart review of SCD patients who presented to the Royal Children's Hospital over a 10.5-year period. Descriptive analyses were conducted., Results: Thirty-seven SCD patients aged from 0.2 to 18.0 years (mean: 8.5 ± 4.8 years) had 535 admissions over the 10.5-year period. The population was made up of 28 homozygous sickle-cell disease, 1 sickle C disease and 8 sickle-cell beta patients from a variety of ethnic backgrounds. Admissions included 264 unplanned admissions, that is 258 admissions via the emergency department and 6 admissions via outpatients, and 271 planned admissions. Mean length of stay for unplanned admissions was 3.2 ± 2.6 days. Common diagnoses for unplanned admissions were 187 vaso-occlusive crisis (70.8%), 32 infections (12.1%) and 26 anaemic episodes (9.8%). Transfusion therapy (91.9%) accounted for the majority of planned admissions., Conclusions: Children with sickle-cell disease in an Australian setting require hospitalisation for various reasons related to disease, either unexpected complications or elective procedures. Factors affecting the provision of optimal healthcare to be explored include the multicultural demographics of the SCD population, the timely management of vaso-occlusive crises and the availability of SCD-related protocols., (© 2012 The Authors. Journal of Paediatrics and Child Health © 2012 Paediatrics and Child Health Division (Royal Australasian College of Physicians).)

β-Thalassemia (β-thal) is a hereditary disease with at least 200 known causative molecular defects, with a limited number of distinct mutations predominating in any given population. The Brazilian population is one of the most heterogeneous in the world. Although occurrences of β-thal in this country have been recognized for a long time and previous studies have shown important regional differences related to the mutational profile, no extensive analysis of mutations of the HBB gene has been carried out in Brazil. We examined 1011 teenagers from Bahia, a state located in the northeast of Brazil. Hematological data were obtained using automated cell counting, hemoglobin (Hb) profiles were studied by high performance liquid chromatography (HPLC), and DNA was analyzed by automated sequencing. None of the four Mediterranean mutations that are most frequently found in South and Southeast Brazil (HBB: c.118C>T; HBB: c.93-21G>A; HBB: c.92+1G>A; HBB: c.92+6T>C), was found to be responsible for thalassemia in the cases that we studied. One heterozygote for a frameshift mutation at codon 44 (-C) was identified. This is the first study to determine the prevalence and profile of β-thal in Bahia State. For the first time in Brazil, we report the occurrence of the HBB: c.135delC mutation in the β-globin gene.

Hereditary persistence of fetal hemoglobin (HPFH) and δβ-thalassemia (δβ-thal) are heterogeneous disorders caused by deletions within the β-globin gene cluster. When combined with other β-thal mutations or structural hemoglobin (Hb) variants, these deletions give rise to clinical phenotypes ranging from an asymptomatic condition to β-thal major (β-TM). Overlap in hematological parameters and variability in expression of Hbs A2 and F make molecular testing necessary to distinguish clinically relevant deletions. Multiplex ligation-dependent probe amplification (MLPA) was used to screen for β-globin gene cluster deletions in 49 unresolved samples referred for a suspected β-thal anomaly. The 1.39 kb Black β(0), 3.5 kb Thai β(0), 118 kb Filipino β(0), 11.8 kb Black (δβ)(0), 13.4 kb Sicilian (δβ)(0), 35.8 kb Black ((A)γδβ)0, Hb Lepore-Boston-Washington (Hb LBW) and HPFH-2 deletions, and two novel deletions, a 61.7 kb Pakistani β(0) deletion and an ((A)γδβ)(0) deletion, were identified in 15 cases. Detection of both known and unknown deletional Hb disorders provides for appropriate clinical management and genetic counseling.

Background: Hemoglobinopathies are the most common inherited diseases in southern China. However, there have been only a few epidemiological studies of hemoglobinopathies in Guangdong province., Materials and Methods: Peripheral blood samples were collected from 15299 "healthy" unrelated subjects of dominantly ethnic Hakka in the Meizhou region, on which hemoglobin electrophoresis and routine blood tests were performed. Suspected cases with hemoglobin variants and hereditary persistence of fetal hemoglobin (HPFH) were further characterized by PCR, DNA sequencing, reverse dot blot (RDB) or multiplex ligation-dependent probe amplification (MLPA). In addition, 1743 samples were randomly selected from the 15299 subjects for thalassemia screening, and suspected thalassemia carriers were identified by PCR and RDB., Results: The gene frequency of hemoglobin variants was 0.477% (73/15299). The five main subgroups of the ten hemoglobin variants were Hb E, Hb G-Chinese, Hb Q-Tahiland, Hb New York and Hb J-Bangkok. 277 cases (15.89%, 277/1743) of suspected thalassemia carriers with microcytosis (MCV<82 fl) were found by thalassemia screening, and were tested by a RDB gene chip to reveal a total of 196 mutant chromosomes: including 124 α-thalassemia mutant chromosomes and 72 β-thalassemia mutant chromosomes. These results give a heterozygote frequency of 11.24% for common α and β thalassemia in the Hakka population in the Meizhou region. 3 cases of HPFH/δβ-thalassemia were found, including 2 cases of Vietnamese HPFH (FPFH-7) and a rare Belgian( G)γ((A)γδβ)⁰-thalassemia identified in Chinese., Conclusions: Our results provide a detailed prevalence and molecular characterization of hemoglobinopathies in Hakka people of the Meizhou region. The estimated numbers of pregnancies each year in the Meizhou region, in which the fetus would be at risk for β thalassemia major or intermedia, Bart's hydrops fetalis, and Hb H disease, are 25 (95% CI, 15 to 38), 40 (95% CI, 26 to 57), and 15 (95% CI, 8 to 23), respectively.

Hemoglobinopathies are a group of inherited single-gene disorders found commonly in the Mediterranean region, Middle East, Indian subcontinent, Burma, and South East Asia. As many as 229 mutation variants of β-thalassemia are reported in the world, many community/region-specific mutations. Very little on thalassemia has been reported in Manipur, a North Eastern Indian state. Thus, a community genetic approach through population screening can be applied to the people of Manipur and a total of 602 blood samples from unrelated Meitei Brahmins (n=300) and Meitei Muslims (n=302) were screened for abnormal hemoglobins by Naked Eye Single Tube Red Cell Osmotic Fragility Test (NESTROFT). HBA(2) level was estimated by using high-performance liquid chromatography and molecular analysis was done by using PCR. Sequencing was also carried out to confirm the mutations. High frequencies of NESTROFT positive (10%) and NESTROFT doubtful (11%) cases were found among the Meitei Brahmins in comparison to the Meitei Muslims [NESTROFT positive (3.31%) and NESTROFT doubtful (1.33%)]. The allele frequency of HB*E was 0.022 and 0.012 among the Meitei Brahmin and Meitei Muslim, respectively. Sequencing of the β-globin gene confirmed a very rare β-thalassemia [-90 C→T (0.33%)] among the Meitei Brahmins of Manipur. This mutation with hemoglobin E in one of the present population hints the presence of the Mongoloid stock among them, possibly from China. There is a need for further studies on other populations of Manipur and the neighboring North East Indian states using such genetic markers.

Catalase decreases the high, toxic concentrations of hydrogen peroxide but it lets the physiological, low concentrations in the cells mainly for signaling purposes. Its decreased activity may contribute to development of several pathological conditions. Catalase mutations occur frequently in exon 9, these were examined with different, complicated and costly methods. The aim of the current study was to evaluate a method for screening of polymorphisms in catalase exon 9. We used the slab gel electrophoresis of PCR amplicons without denaturation and silver staining for visualization of the DNA bands. We detected extra DNA bands in the 400-800 bp region of the catalase exon 9. Their single stranded nature was proved with nucleotide sequence analyses, comparison with the standard SSCP, staining with Sybr Green II and Sybr Green I, ethidium bromide, no digestion with RFLP (BstX I), and digestion with plant nuclease. We used this method for examination of polymorphisms of catalase exon 9 in microcytic anemia and beta-thalassemia patients. The lowest blood catalase activities were detected in microcytic anemia and beta-thalassemia patients with the TT genotypes of the C111T polymorphism. This method was sensitive for detection of G113A acatalasemia mutation, but poorly detected C37T and G5A acatalasemia mutations., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The α-thalassemia-1 (α-thal-1) Southeast Asian (- -(SEA)) type deletion, β-thalassemia (β-thal) and Hb E [β26(B8)Glu→Lys, GAG>AAG] are the most common genetic disorders in Southeast Asian populations. Mean corpuscular volume (MCV) <80.0 fL with normal hemoglobin (Hb) is used for screening α- and β-thal, and a Hb E level of less than 25.0% is used for predicting α-thal-1 in Hb E trait. Thus, levels of Hb, MCV and Hb A(2)/E were reviewed and compared between the SEA type deletion co-inherited with β-thal trait (n = 61), with Hb E trait (n = 102) or homozygous Hb E (n = 13) and β-thal trait (n = 636), Hb E trait (n = 544) or homozygous Hb E (n = 83), respectively. When comparing the values of all three analyzed hematological parameters, only the - -(SEA)/β(E) values were shown to be significantly lower than those of Hb E trait. Furthermore, at a cut-off value of Hb A(2)/E of 21.54%, 95.0% of the - -(SEA)/β(E) had Hb A(2)/E levels lower than this cut-off value, while 94.0% of Hb E trait had Hb A(2)/E at higher levels. Accordingly, the Hb A(2)/E level at 21.54% is the best indicator for predicting co-inheritance of the α-thal-1 - -(SEA)/ deletion and Hb E trait.

Fetal hemoglobin (Hb F) is characteristic of the fetal development period. However, in some genetic conditions, such as hereditary persistence of fetal hemoglobin (HPFH) and delta-beta thalassemia (δβ-thalassemia), Hb F continues to be produced in adulthood. We evaluated the frequency of two mutations of HPFH, HPFH-1 and HPFH-2 African, and two mutations in δβ-thalassemia, Sicilian and Spanish, in a Brazilian population. Peripheral blood samples were collected from adults from hospitals and blood centers in southeast and northeast Brazil. These individuals were healthy and without complaints of anemia, but had increased Hb F. Samples were submitted to electrophoretic and chromatographic analyses to quantify Hb F values and, subsequently, to molecular analyses to verify the mutations. In the molecular analysis, 16 of the 60 samples showed a heterozygous profile for the HPFH mutations, two for HPFH-1 and 14 for HPFH-2. In the same sample set, three were heterozygous for Spanish δβ-thalassemia and none were heterozygous for Sicilian δβ- thalassemia. The Hb F values in the HPFH-2 heterozygotes differed from those previously reported for this mutation. In this group, the HPFH mutations were more frequent than the δβ-thalassemia mutations. The finding of these mutations in this Brazilian population reflects the mixing process that occurred during its formation.

Background: Sickle cell disease (SCD) occurs in 1 of every 500 African American births and 1 of every 36,000 Hispanic American births. Of children with SCD, 16.7% to 96.3% develop sickle retinopathy (SR). This study was designed to determine whether certain factors are associated with SR and whether SR is correlated with a greater incidence of other SCD manifestations., Methods: A retrospective analysis was performed of 258 children with SCD seen in the ophthalmology clinic at a large urban children's hospital. Of these, 54 children with SR were matched for age and sickle variant with 54 children with normal examinations. Data extracted included demographics, type of retinopathy, presence of glucose-6-phosphate dehydrogenase (G6PD) deficiency, and history of acute chest syndrome, transfusions, pulmonary hypertension, renal disease, cerebrovascular accident, aplastic crisis, splenic sequestration, priapism, osteonecrosis, gallstones, pneumonia, leg ulcers, vaso-occlusive pain crises, and death., Results: Of the children with SR, 11 (20.3%) had active proliferative disease, 32 (56.1%) had hemoglobin SS, 18 (31.6%) had hemoglobin SC, and 4 (7.0%) had hemoglobin S-beta thalassemia. Several factors were correlated with retinopathy: pain crisis (odds ratio [OR], 5.00; p=0.011), male sex (OR, 4.20, p=0.004), and splenic sequestration (OR, 4.00; p=0.013). G6PD deficiency was more common in patients with retinopathy, although this was not statistically significant (OR, 4.20; p=0.054). No other factors, including frequency of pain crisis, were statistically significant., Conclusions: Patients with pain crisis and splenic sequestration should be considered for early ophthalmic evaluation. Those with G6PD deficiency may also deserve early screening. By identifying patients at high risk for SR, we can refine screening protocols to safeguard patients from vision loss., (Copyright © 2011 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.)

To assess alpha+-thalassemia deletion alleles, beta-thalassemia mutations and haplotypes linked to the HBB*S cluster in a sample of 130 unrelated sickle cell anemia (SCA) patients (55% female) from Belém, Pará State, for their possible effects on the patients' survival. -alpha(3.7), -alpha(42), -alpha(20.5), and -(MED) alpha+-thalassemia deletion alleles were investigated using multiplex gap-PCR method. Characterization of beta-thalassemia mutations was made by direct genomic sequencing of the beta-globin gene amplified through polymerase chain reaction (PCR). Haplotypes were determined by analysis of six polymorphic restriction sites [(1) XmnI-5'gammaG, (2) HindIII-gammaG, (3) HindIII-gammaA, (4) HincII-psibeta, (5) HincII-3'psibeta, and (6) HinfI-5'beta] followed by restriction digestion and agarose gel electrophoresis. Twenty-one patients (16%) presented -alpha3.7 thalassemia. Sixteen of those (76%) were heterozygous (-alpha3.7/alphaalpha) and 5 (24%) were homozygous (-alpha3.7/-alpha3.7). -Alpha(4.2), -alpha(20.5) and -(MED) deletions were not found. Nine cases of sickle cell-beta thalassemia were found and four different beta-thal mutations were identified: beta(+) -88 (C>T), 3.8%; beta(+) codon 24 (T > A), 1.5%; beta(+) IVSI-110 (G > A), 0.7% and beta (IVSI-1 (G > A), 0.7%. No differences according to age were observed in -alpha(3.7) deletion, beta-thalassemia and HHB*S haplotypes distribution. Our results suggest that although alpha- and beta-thalassemia and betaS haplotypes may have modulating effect on clinical expression and hematological parameters of SCA, these genetic variables probably have little influence on the subjects' survival., ((c) 2010 Wiley-Liss, Inc.)

This molecular genetics study was conducted in Karachi, Pakistan from 2004 to 2006 to provide guidelines for prenatal diagnosis programmes in the country. Blood samples of patients with beta-thalassaemia minor (n=200) and beta-thalassaemia major (n=150) were collected from hospitals, transfusion centres and diagnostic laboratories from different districts of Karachi, representing 5 major ethnic groups. Molecular analysis revealed 11 genetic mutations of the beta-thalassaemia gene, among which 5 mutations accounted for 88% of the total beta-thalassaemia genes identified [IVS-1-5 (G-C), Fr 8/9 (+G), Fr 41/42 (-TTCT), IVS-1-1 (G-T) and Del 619]. Other mutations identified were: CAP+1 IVS-II-1 (G-A), Cd 5 (-CT), Cd 15 (G-A). Cd 16 and Cd 30.

In order to obtain an approximate assessment of the public health burden that will be posed by the inherited disorders of haemoglobin in southern Vietnam, several thousand individuals were screened for these conditions. A smaller sample was screened for glucose-6-phosphate dehydrogenase (G6PD) deficiency. The important haemoglobin disorders identified were beta thalassaemia, haemoglobin E and a variety of different forms of alpha thalassaemia. There were sufficient G6PD-deficient individuals to materially affect malaria control programme design. The most remarkable finding was wide variation in the gene frequencies of these conditions among the ethnic groups sampled. The approximate number of babies expected to be born with clinically significant haemoglobin disorders in Vietnam was estimated from the gene-frequency data. This study emphasizes the importance of wide-scale population screening, including ethnic subgroups, to establish the requirements for inherited haemoglobin disorder programmes in resource-limited settings.

Introduction and Aims: Bangladesh has a large number of thalassemic patients. However, no extensive analysis of the mutations in the HBB gene of thalassemic patients has been previously carried out. We have conducted a systematic research to reveal thalassemia mutations in the Bangladeshi population. In this preliminary analysis of 587 bp of the HBB gene in selected thalassemic individuals, some rare mutations in world perspective have been found to be significantly high in the Bangladeshi population, together with the common mutations for thalassemia., Results: A 587-bp segment of the HBB gene from 32 chromosomes of 16 beta-thalassemic individuals was analyzed for molecular characterization of the disease. Splice junction mutation IVS-I-5 was found to be the most common. The analysis also revealed some rare mutations HBB: c.-80T>C, HBB: c. 92G>C, HBB: c-92C>G, which are not prevalent in geographically adjacent populations., Conclusion: This is a first of this kind of study in the Bangladeshi population. Although the small sample size makes it difficult to make any population genetics inference, this study can be regarded as the seminal research for a large-scale study to determine the complete mutation profile underlying thalassemia in the Bangladeshi population. The complete mutation profile will provide invaluable strategies (e.g., prenatal diagnosis and genetic counseling) for better management of thalassemia in the Bangladeshi population.

Current methods that assay hemoglobin beta-globin chain variants can have limited clinical sensitivity when applied techniques identify only a predefined panel of mutations. Even sequence-based assays may be limited depending on which gene regions are investigated. We sought to develop a clinically practical yet inclusive molecular assay to identify beta-globin mutations in multicultural populations. We highlight the beta-globin mutation detection assay (beta-GMDA), an extensive gene sequencing assay. The polymerase chain reaction (PCR) primers are located to encompass virtually all hemoglobin beta locus (HBB) mutations. In addition, this assay is able to detect, by gap PCR, a common large deletion (Delta619 base pair), which would be missed by sequencing alone. We describe our 5-year experience with the beta-GMDA and indicate its capability for detecting homozygous, heterozygous, and compound heterozygous sequence changes, including previously unknown HBB variants. The beta-GMDA offers superior sensitivity and ease of use with comprehensive detection of HBB mutations that result in beta-globin chain variants.