Incidence of haemoglobinopathies in various populations — The impact of immigration

Henderson, Shirley; Timbs, Adele; McCarthy, Janice; Gallienne, Alice; Mourik, Margaretha Van; Masters, Gillian S.; May, Alison; Khalil, Mohamed S; Schuh, Anna; Old, John

doi:10.1016/j.clinbiochem.2009.05.012

Cited by 53 publications

(47 citation statements)

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“…& IVS-1-6 was found to be associated with multiple haplotypes in Lebanon (VI, VII and I) compared with its relative homogeneity in European populations where it is also frequently encountered, suggesting a possible ancient Eastern Mediterranean origin (Flint et al 1993;Makhoul et al 2005). & IVS-1-1 has its highest frequency in eastern Europe (Henderson et al 2009) and it is seen in association with haplotype V in Lebanon and Palestinian Arabs but with multiple haplotypes including V in North Africa probably reflecting independent origins in these two parts of the Arab world (El-Latif et al 2002;Haj Khelil et al 2010;Makhoul et al 2005). & IVS-II-1 has been linked to different haplotypes in various parts of the world.…”

Section: Introductionmentioning

confidence: 99%

Epidemiological profile of common haemoglobinopathies in Arab countries

2012

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Haemoglobinopathies including the thalassemias and sickle cell disease are known to be prevalent inherited disorders in most Arab countries with varying prevalence rates and molecular characterisation. β-thalassemia is encountered in polymorphic frequencies in almost all Arab countries with carrier rates of 1-11 % and a varying number of mutations. The most widespread mutation in Lebanon, Egypt, Syria, Jordan, Tunisia and Algeria is the IVS-I-110 (G>A). In the Eastern Arabian Peninsula, the Asian Indian mutations (IVS-I-5 (G>C), codons 8/9 (+G) and IVS-I (−25 bp del)) are more common. The α-thalassemias are encountered in the majority of Arab countries in frequencies ranging from 1 to 58 % with the highest frequencies reported from Gulf countries. The (−α 3.7 ) mutation is the most frequent followed by the non-deletional α2 polyadenylation signal mutation (AATAAA>AATAAG) and the α2 IVS1 5-bp deletion. The rates of sickle cell trait in Arab countries range from 0.3 to 30 %, with the Benin, the Arab-Indian and the Bantu haplotypes constituting the bulk of the haplotypes, leading to two major phenotypes; a mild one associated with the Arab-Indian and a severe one with the Benin and Bantu haplotypes. Public health approaches targeting prevention of haemoglobinopathies in Arab countries include newborn screening for sickle cell disease, and premarital screening for carriers of β-thalassemia and sickle cell disease. These services are still patchy and inadequate in many Arab countries recommending the upgrade of these services with strengthening of the education and training of health care providers and raising public awareness on the feasibility of prevention and care for haemoglobinopathies.

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Section: Introductionmentioning

confidence: 99%

Epidemiological profile of common haemoglobinopathies in Arab countries

2012

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“…In the UK it is becoming evident that non-deletional α-thalassaemia mutations are found in a wider spectrum of the population than previously thought, with the discovery of 30 different mutations out of the known published worldwide total of 67 non-deletion mutations (46%) [8]. This gives the UK the widest range of α-thalassaemia mutations of any country with a published spectrum of mutations.…”

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confidence: 90%

“…There are ten non-deletional α-thalassaemia mutations that are clinically significant and 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 V6 3 relatively common within the UK population [8]. 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, Quong Sze and Adana (table 1).…”

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Screening for clinically significant non-deletional alpha thalassaemia mutations by pyrosequencing

et al. 2010

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Non-deletional alpha plus thalassaemia is associated with a higher degree of morbidity and mortality than deletional forms of alpha plus thalassaemia. Screening for the common deletional forms of alpha-thalassaemia by Gap-PCR is widely practiced; however the detection of non-deletional alpha 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 alpha-thalassaemia present another layer of complexity in the detection of these mutations. With growing evidence that non-deletional alpha-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 alpha-thalassaemia mutations in the UK. We tested 105 patients with non-deletional alpha-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 alpha-thalassaemia. The technique is also likely to help expedite prenatal diagnosis of pregnancies at risk of alpha-thalassaemia major. AbstractNon-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 -thalassaemia present another layer of complexity in the detection of these mutations. With growing evidence that nondeletional 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 -thalassaemia. The technique is also likely to help expedite prenatal diagnosis of pregnancies at risk of α-thalassaemia major.

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“…Each country in its group has a spectrum of abnormal haemoglobins and thalassaemia mutations, consisting of a few common alleles and a larger number of alleles found at much lower gene frequencies. The spectrum and frequency of haemoglobinopathy mutations, especially those for β-thalassaemia, have now been determined for most countries [3].…”

Section: Introductionmentioning

confidence: 99%

New Challenges in Diagnosis of Haemoglobinopathies: Migration of Populations

Old¹,

Timbs²,

McCarthy³

et al. 2018

Thalassemia Reports

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The current influx of economic migrants and asylum seekers from countries with a high prevalence of haemoglobinopathies creates new challenges for health care systems and diagnostic laboratories. The migration of carriers introduces new and novel haemoglobinopathy mutations to the diagnostic repertoire of a laboratory, often creating new pressures to improve and update the carrier screening technology and diagnostic scope. For antenatal screening programmes, the marriage of partners from different ethnic groups can lead to the risk of compound heterozygote children being born novel mutation combinations, creating problems in the provision of accurate advice regarding the expected phenotype of the thalassaemia or haemoglobinopathy disorder. In the UK, the impact of immigration required the National Haemoglobinopathy Reference laboratory to change the strategy and techniques used for the molecular diagnosis of thalassaemia and the haemoglobinopathies. In 2005, due to the increasingly large range of β-thalassaemia mutations that needed to be diagnosed, the laboratory switched from a three-step screening procedure using ARMS-PCR to a simpler but more expensive one-step strategy of DNA sequencing of the beta and alpha globin genes for all referrals. After ten years of employing this strategy, a further 57 novel thalassaemia and haemoglobionpopthy alleles were discovered (11 new β-chain variants, 15 α-chain variants, 19 β-thalassaemia mutations and 12 α + -thalassaemia mutations), increasing further the extremely heterogeneous spectrum of globin gene mutations in the UK population.

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Incidence of haemoglobinopathies in various populations — The impact of immigration

Cited by 53 publications

References 72 publications

Epidemiological profile of common haemoglobinopathies in Arab countries

Epidemiological profile of common haemoglobinopathies in Arab countries

Screening for clinically significant non-deletional alpha thalassaemia mutations by pyrosequencing

New Challenges in Diagnosis of Haemoglobinopathies: Migration of Populations

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