Incidence of haemoglobinopathies in various populations—the impact of immigration. Clin Biochem
ABSTRACT The aim of this study was to update the incidence data of beta thalassaemia mutations in various populations and compare it to the spectrum of mutations in the United Kingdom (UK) population in order to determine the impact of immigration.
Published data for the beta-thalassaemia mutation spectrum and allele frequencies for 60 other countries was updated and collated into regional tables. The beta-thalassaemia mutations in the UK population have been characterised in 1712 unrelated carriers referred for antenatal screening. Similarly, the alpha-thalassaemia mutations in the UK population have been characterised in 2500 possible alpha-thalassaemia carriers.
A total of 68 different beta-thalassaemia mutations were identified in couples requiring screening for antenatal diagnosis in the UK population. Of these mutations, 59 were found in immigrants to the UK, from all major ethnic groups with a high incidence of haemoglobinopathies. A total of 40 different alpha-thalassaemia mutations were characterised in the UK population. Ten deletion mutations were identified, including all the Southeast Asian and Mediterranean alpha(0)-thalassaemia mutations. In addition, 30 non-deletion alpha(+)-thalassaemia mutations were discovered, accounting for 46% of the worldwide known non-deletion mutations.
The impact of immigration has resulted in the UK population having a higher number of beta-thalassaemia mutations and alpha-thalassaemia mutations than any of the 60 other countries with a published spectrum of mutations, including both endemic countries and the non-endemic countries of Northern Europe. The racial heterogeneity of the immigrant population in a non-endemic country significantly increases the spectrum of haemoglobinopathy mutations and their combinations found in individuals, making the provision of a molecular diagnostic prenatal diagnosis service more challenging.
- SourceAvailable from: Petros Kountouris
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- "Hb disorders comprise the thalassaemias, sickle-cell disease, Hb E and other, rarer disorders and are prevalent in former malaria regions in the Mediterranean, the Middle East, South-East Asia and Sub-Saharan Africa . However, demographic events, such as migration and the consequent intermixing of populations, have contributed to the spread of Hb disorders worldwide , . Therefore, the prevalence of Hb disorders is rising in non-endemic regions, such as Northern and Western Europe and North America, posing a major challenge for researchers and health professionals. "
ABSTRACT: Inherited haemoglobinopathies are the most common monogenic diseases, with millions of carriers and patients worldwide. At present, we know several hundred disease-causing mutations on the globin gene clusters, in addition to numerous clinically important trans-acting disease modifiers encoded elsewhere and a multitude of polymorphisms with relevance for advanced diagnostic approaches. Moreover, new disease-linked variations are discovered every year that are not included in traditional and often functionally limited locus-specific databases. This paper presents IthaGenes, a new interactive database of haemoglobin variations, which stores information about genes and variations affecting haemoglobin disorders. In addition, IthaGenes organises phenotype, relevant publications and external links, while embedding the NCBI Sequence Viewer for graphical representation of each variation. Finally, IthaGenes is integrated with the companion tool IthaMaps for the display of corresponding epidemiological data on distribution maps. IthaGenes is incorporated in the ITHANET community portal and is free and publicly available at http://www.ithanet.eu/db/ithagenes.PLoS ONE 07/2014; 9(7):e103020. DOI:10.1371/journal.pone.0103020 · 3.23 Impact Factor
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- "The synthesis of structurally abnormal globin chains, on the other hand, causes abnormal hemoglobins, and the substitution of a single nucleotide for another is suggested to be the most common genetic alteration that results in hemoglobin variants . Sickle hemoglobin (Hb S), for example, is caused by the replacement of glutamic acid by valine in the 6th codon of the β-globin chain, and sickle cell disease (SCD) affects millions throughout the world . "
ABSTRACT: The frequency of hemoglobinopathies is still high in Adana, the biggest city of the Cukurova Region that is located in the southern part of Turkey. Our aim was to identify the concomitant mutations in α- and β-globin genes which lead to complex hemoglobinopathies and to establish an appropriate plan of action for each subject, particularly when prenatal diagnosis is necessary. We studied the association between the β-globin gene and α-thalassemia genotypes. The reverse hybridization technique was employed to perform molecular analysis, and the results were confirmed by amplification refractory mutation system (ARMS) or restriction fragment length polymorphism (RFLP) technique. We evaluated 36 adult subjects (28 female and 8 male; age range: 18-52 years) with concomitant mutations in their α- and β-globin genes. The -α(3.7)/αα deletion was the commonest defect in the α-chain as expected, followed by α(3.7)/-α(3.7) deletion. Twenty-five of 36 cases were sickle cell trait with coexisting α-thalassemia, while seven Hb S/S patients had concurrent mutations in their α-genes. The coexistence of α(PolyA-2)α/αα with Hb A/D and with Hb S/D, which is very uncommon, was also detected. There was a subject with compound heterozygosity for β-globin chain (-α(3.7)/αα with IVSI.110/S), and also a case who had -α(3.7)/αα deletion with IVSI.110/A. Although limited, our data suggest that it would be valuable to study coexisting α-globin mutations in subjects with sickle cell disease or β-thalassemia trait during the screening programs for premarital couples, especially in populations with a high frequency of hemoglobinopathies.09/2012; 8(4):644-9. DOI:10.5114/aoms.2012.28723
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- "Six beta-thalassemia trait mutations (IVS-I-110 G>A, CD 31 G>C, CD 90 G>T, CD 41- TCTT, CAP+20 C>T, CD 2 A>T) have not been reported for Hungarian beta-thalassemia ++ patients but they were detected in other European countries (Henderson et al., 2009). These beta-thalassemia trait mutations may be of Mediterranean origin and may reflect the impact of migration (Henderson et al., 2009). "
ABSTRACT: Thalassemia erythrocytes are exposed to oxidative stress especially to hydrogen peroxide, which is regulated with the enzyme catalase. The aim of this study was to examine blood catalase activity and the relationship of blood catalase and beta-thalassemia gene mutations. Blood catalase activity, hemoglobin, HbA(2) , HbF, and beta-globin gene mutations were determined in 43 Hungarian patients with beta-thalassemia trait. Compared to controls, the beta-thalassemia trait patients showed a low mean (P < 0.001) of blood catalase (men: 84 ± 29 MU/L vs. sex-matched controls: 118 ± 18 MU/L and women: 74 ± 18 MU/L vs. 108 ± 114 MU/L) and a low mean of blood catalase-to-blood hemoglobin ratio (men: 0.72 ± 0.22 MU/g vs. 0.85 ± 0.12 MU/g, women: 0.77 ± 0.26 MU/g vs. 0.84 ± 0.11 MU/g). The HbA(2) determination showed high sensitivity and specificity for the detection of beta-thalassemia trait patients. Mutation analyses revealed 13 beta-thalassemia trait mutations, of which six have not been reported before in Hungarian beta-thalassemia trait patients. Each group of mutations revealed decreased (P < 0.01) mean of blood catalase and catalase-to-hemoglobin ratio. Acatalasemia mutations were not found in beta-thalassemia trait patients. The decrease in blood catalase activity might be due to the damaging effects of free radicals on the catalase protein. Consequently, these beta-thalassemia trait patients may be relatively susceptible to damage caused by oxidative stress.International journal of laboratory hematology 04/2012; 34(2):172-8. DOI:10.1111/j.1751-553X.2011.01377.x · 1.82 Impact Factor