Incidence of haemoglobinopathies in various populations - The impact of immigration
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: Laszlo Góth
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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 · 1.87 Impact Factor
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- "There are ten non-deletional α-thalassaemia mutations that are clinically significant and V6 3 relatively common within the UK population . These mutations consist of the α2 termination codon mutations (Hb Constant Spring, Hb Paksé, Hb Icaria, and Hb Seal Rock), the α2 polyadenylation signal mutations (Saudi, Turkish and Indian Mutations), and the mutations which give rise to the hyper unstable alpha globin chain variants Sun Prairie, "
ABSTRACT: Non-deletional α(+)-thalassaemia is associated with a higher degree of morbidity and mortality than deletional forms of α(+)-thalassaemia. Screening for the common deletional forms of α-thalassaemia by Gap-PCR is widely practiced; however, the detection of non-deletional α-thalassaemia mutations is technically more labour-intensive and expensive, as it requires DNA sequencing. In addition, the presence of four very closely homologous alpha globin genes and the frequent co-existence of deletional forms of α-thalassaemia present another layer of complexity in the detection of these mutations. With growing evidence that non-deletional α-thalassaemia is relatively common in the UK, there is a demand for technologies which can quickly and accurately screen for these mutations. We describe a method utilising pyrosequencing for detecting the ten most common clinically significant non-deletional α-thalassaemia mutations in the UK. We tested 105 patients with non-deletional α-thalassaemia and found 100% concordance with known genotype as identified by Sanger sequencing. We found pyrosequencing to be simpler, more robust, quicker, and cheaper than conventional sequencing, making it a good choice for rapid and cost-effective diagnosis of patients with suspected non-deletional α-thalassaemia. The technique is also likely to help expedite prenatal diagnosis of pregnancies at risk of α-thalassaemia major.Annals of Hematology 12/2010; 89(12):1215-21. DOI:10.1007/s00277-010-1013-2 · 2.40 Impact Factor
Conference Paper: Measurements of the radiation belts from Mir and STRV 1994-1997[Show abstract] [Hide abstract]
ABSTRACT: Simple environment monitors were launched in 1994; one was placed in geostationary transfer orbit (GTO) onboard STRV-1b while the second was installed externally on Mir in LEO. GTO covers the equatorial regime of the inner and outer radiation belts well. Mir encounters the belts near atmospheric cut-off. We summarize these observations. The outer (electron) belt has been subject to many injection events, including during January 1997. Mir data show the strong anisotropy in the low-altitude inner (proton) belt. Results are compared with modelsHigh Energy Radiation Background in Space, 1997 Conference on the; 08/1997