Elderdery A.Y.,University of Portsmouth |
Elderdery A.Y.,El University of Imam El Mahdi |
Mills J.,University of Portsmouth |
Cooper A.J.,University of Portsmouth |
And 2 more authors.
International Journal of Laboratory Hematology
Introduction: Sudan has a multiethnic population with a high frequency of Hb S, but little is known about the β S haplotypes in this population. Methods: Blood samples from Sudanese Hb SS individuals were taken at two locations. Family history, age, ethnicity and clinical symptoms were recorded for each subject. Hb S was investigated using cellulose acetate electrophoresis (CAE) and cation exchange-high performance liquid chromatography. Dried blood samples from 93 individuals were used for β S haplotype identification based on restriction fragment length polymorphism analysis for seven restriction sites. Results: Haplotypes could be assigned unequivocally to 143 chromosomes. Four of the five typical β S-globin haplotypes were identified. The most frequent was the Cameroon (35.0%), followed by the Benin (29.4%), the Senegal (18.2%) and the Bantu (2.8%). The Indian-Arab haplotype was not observed. Three atypical haplotypes were identified in 17 patients, occurring at a combined frequency of 14.6%. One of these, found at the high frequency of 11.8%, possibly represented a new Sudan haplotype. Conclusion: β S Haplotyes were demonstrated successfully from dried blood samples. A new haplotype is apparent in Sudan, in addition to the four African haplotypes. © 2012 Blackwell Publishing Ltd. Source
Khalil M.S.M.,Oxford Molecular Diagnostic Center |
Marouf S.,Oxford Molecular Diagnostic Center |
Element D.,St. Georges Hospital |
Timbs A.,Oxford Molecular Diagnostic Center |
And 5 more authors.
We report here the spectrum of δ-globin gene mutations found in the UK population. Nine different δ chain variants and two δ-thalassemia (δ-thal) mutations were characterized in a study of 127 alleles in patients with either a low Hb A2 value or a split Hb A2 peak on high performance liquid chromatography (HPLC). The most common δ chain variant was Hb (or Hb B2) [δ16(A13)Gly→Arg; HBD: c.49G>C] (77.0%), followed by Hb A2-Yialousa [δ27(B9)Ala→Ser; HBD: c.82G>T] (12.0%), Hb A2-Babinga [δ136(H14)Gly→Asp; HBD: c.410G>A] (3.0%), Hb A2-Troodos [δ116(G18)Arg→Cys; HBD: c.349C>T] (1.0%), Hb A2-Coburg [δ116(G18)Arg→His; HBD: c.350G>A] (2.0%) and Hb A2-Indonesia [δ69(E13)Gly→Arg; HBD: c.208G>C] (1.0%). Three novel variants were identified: Hb A2-Calderdale [codon 2 (CAT>AAT), His→Asn; HBD: c.7C>A], Hb A2-Walsgrave [codon 52 (GAT>CAT), Asp→His; HBD: c.157G>C] and Hb A2-St. George's [codon 81 (CTC>TTC), Leu→Phe; HBD: c.244C>T]. In addition, two known δ-thal mutations were observed: -68 (C>T); HBD: c.-118C>T and codon 4 (ACT>ATT); HBD: c.14C>T. Amplification refractory mutation system (ARMS) primers were developed to provide a simple molecular diagnostic test for the most common variant, Hb . Three of the variants had a characteristic HPLC retention time that can be used for a presumptive diagnosis. © 2014 Informa Healthcare USA, Inc. Source
Old J.,National Haemoglobinopathy Reference Laboratory |
Henderson S.,National Haemoglobinopathy Reference Laboratory
Expert Opinion on Medical Diagnostics
Importance of the field: The globin gene mutations have been used as a prototype for the development of many techniques of mutation detection for >30 years, and consequently there have been numerous PCR-based methods described that can be used for the molecular diagnosis of the haemoglobinopathies. Areas covered in this review: This review describes the most commonly used current methods for the detection of each of the different types of thalassaemia mutation and abnormal haemoglobin, and reviews the most promising newer technology. In addition, it outlines the various diagnostic strategies commonly used for prenatal diagnosis by fetal DNA analysis and discusses the state of progress of the molecular analysis of cell-free DNA for non-invasive prenatal diagnosis. What the reader will gain: An understanding of which are the best current techniques for carrier detection and prenatal diagnosis of the full range of haemoglobinopathy mutations, and which of the newer, more complex technologies are being applied to the emerging approach of non-invasive prenatal diagnosis of beta thalassaemia and sickle cell disease. Take home message: The haemoglobinopathies are a very heterogeneous group of genetic disorders with >1300 different mutations described, from point mutations to large deletions and complex gene rearrangements. Despite the complexity of the disorders and the plethora of high-tech diagnostic methods developed, mutation screening and prenatal diagnosis are still carried out in many countries by simple and cheap in-house methods developed many years ago; however, the more advanced technologies may well play an essential role in the various approaches to non-invasive prenatal diagnosis haemoglobinopathies in the future. © 2010 Informa UK Ltd. Source
Traeger-Synodinos J.,National and Kapodistrian University of Athens |
Harteveld C.L.,Leiden University |
Old J.M.,National Haemoglobinopathy Reference Laboratory |
Petrou M.,University College London |
And 6 more authors.
European Journal of Human Genetics
Haemoglobinopathies constitute the commonest recessive monogenic disorders worldwide, and the treatment of affected individuals presents a substantial global disease burden. Carrier identification and prenatal diagnosis represent valuable procedures that identify couples at risk for having affected children, so that they can be offered options to have healthy offspring. Molecular diagnosis facilitates prenatal diagnosis and definitive diagnosis of carriers and patients (especially 'atypical' cases who often have complex genotype interactions). However, the haemoglobin disorders are unique among all genetic diseases in that identification of carriers is preferable by haematological (biochemical) tests rather than DNA analysis. These Best Practice guidelines offer an overview of recommended strategies and methods for carrier identification and prenatal diagnosis of haemoglobinopathies, and emphasize the importance of appropriately applying and interpreting haematological tests in supporting the optimum application and evaluation of globin gene DNA analysis. © 2015 Macmillan Publishers Limited All rights reserved. Source
Gallienne A.E.,National Haemoglobinopathy Reference Laboratory |
Iberson N.M.,National Haemoglobinopathy Reference Laboratory |
Drau H.M.,National Haemoglobinopathy Reference Laboratory |
Jackson H.,Newtown Health Clinic |
And 4 more authors.
We have identified and characterized a novel β-globin gene deletion mutation in a family of Afghan ancestry. The proband was a 10-year-old transfusion-dependent female with the phenotype of β-thalassemia major (β-TM). DNA sequencing of the β-globin gene showed no abnormalities. Multiplex ligation-dependent probe amplification (MLPA) showed reducedabsent probe height of the probe covering the 5′ end of the β-globin gene indicating a possible deletion. Gap-polymerase chain reaction (gap-PCR) produced junctional fragments and direct sequencing of the product revealed that the 5′ breakpoint was 478 nucleotides upstream of the Cap site and the 3′ breakpoint was in the second exon of the β-globin gene, giving a deletion size of 909 bp. The proband was homozygous and the parents were heterozygous for the deletion. This is the first report of a large β-thalassemia (β-thal) deletion mutation in this ethnic group. © 2010 Informa UK, Ltd. Source