title: A study of δ-globin gene mutations in the UK population: identification of three novel variants and development of a novel DNA test for Hb A'2.
abstract: 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 [Formula: see text] (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 [Formula: see text]. Three of the variants had a characteristic HPLC retention time that can be used for a presumptive diagnosis.
authors.affiliation: Department of Haematology, National Haemoglobinopathy Reference Laboratory, Oxford Molecular Diagnostic Centre, John Radcliffe Hospital , Oxford, Oxfordshire , UK.
authors.forename: Mohamed S M
authors.initials: MS
authors.lastname: Khalil
authors.forename: Samy
authors.initials: S
authors.lastname: Marouf
authors.forename: David
authors.initials: D
authors.lastname: Element
authors.forename: Adele
authors.initials: A
authors.lastname: Timbs
authors.forename: Alice
authors.initials: A
authors.lastname: Gallienne
authors.forename: Anna
authors.initials: A
authors.lastname: Schuh
authors.forename: John M
authors.initials: JM
authors.lastname: Old
authors.forename: Shirley
authors.initials: S
authors.lastname: Henderson
mesh_terms: D004252:DNA Mutational Analysis; D005260:Female; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006801:Humans; D008297:Male; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D009154:Mutation; D006113:United Kingdom / Q000453:epidemiology; D055546:delta-Globins / Q000235:genetics*; D055538:delta-Thalassemia / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics
chemical_list: D006455:Hemoglobins, Abnormal; D055546:delta-Globins
keywords: novel Hb A2 variants; δ-Globin gene mutations