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. (June 2014)

• Record Type: Journal Article
• Authors: Khalil, Mohamed S. M.; Marouf, Samy; Element, David; Timbs, Adele; Gallienne, Alice; Schuh, Anna; Old, John M.; Henderson, Shirley
• Is Part Of: Hemoglobin. Volume 38:Number 3(2014)
• Page Start: 201
• Page End: 206
• Publication Date: 2014-06
• Subjects: Hemoglobinopathy -- Periodicals; Hemoglobin -- Periodicals; Hematology -- Periodicals; Thalassemia -- Periodicals; Blood -- Diseases -- Periodicals; 612.1111
• DOI: 10.3109/03630269.2014.885908
• Languages: English
• ISSNs: 0363-0269

Abstract

<abstract> <title>Abstract</title> <p>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 A<sub>2</sub> value or a split Hb A<sub>2</sub> peak on high performance liquid chromatography (HPLC). The most common δ chain variant was Hb <inline-formula><tex-math notation="TeX"><![CDATA[\def\newpage{\vfill \break } \nopagenumbers $ {\rm A}_2' $ \newpage \end]]></tex-math></inline-formula> (or Hb B<sub>2</sub>) [δ16(A13)Gly → Arg; <italic>HBD</italic>: c.49G > C] (77.0%), followed by Hb A<sub>2</sub>-Yialousa [δ27(B9)Ala → Ser; <italic>HBD</italic>: c.82G > T] (12.0%), Hb A<sub>2</sub>-Babinga [δ136(H14)Gly → Asp; <italic>HBD</italic>: c.410G > A] (3.0%), Hb A<sub>2</sub>-Troodos [δ116(G18)Arg → Cys; <italic>HBD</italic>: c.349C > T] (1.0%), Hb A<sub>2</sub>-Coburg [δ116(G18)Arg → His; <italic>HBD</italic>: c.350G > A] (2.0%) and Hb A<sub>2</sub>-Indonesia [δ69(E13)Gly → Arg; <italic>HBD</italic>: c.208G > C] (1.0%). Three novel variants were identified: Hb A<sub>2</sub>-Calderdale [codon 2 (<italic>C</italic>AT > <italic>A</italic>AT), His → Asn; <italic>HBD</italic>: c.7C > A], Hb A<sub>2</sub>-Walsgrave [codon 52 (<italic>G</italic>AT > <italic>C</italic>AT), Asp → His; <italic>HBD</italic>: c.157G > C] and Hb A<sub>2</sub>-St. George's [codon 81 (<italic>C</italic>TC > <italic>T</italic>TC), Leu → Phe; <italic>HBD</italic>: c.244C > T]. In addition, two known δ-thal mutations were observed: −68 (C > T); <italic>HBD</italic>: c.-118C > T and codon 4 (A<italic>C</italic>T > A<italic>T</italic>T); <italic>HBD</italic>: c.14C > T. Amplification refractory mutation system (ARMS) primers were developed to provide a simple molecular diagnostic test for the most common variant, Hb <inline-formula><tex-math notation="TeX"><![CDATA[\def\newpage{\vfill \break } \nopagenumbers $ {\rm A}_2' $ \newpage \end]]></tex-math></inline-formula>. Three of the variants had a characteristic HPLC retention time that can be used for a presumptive diagnosis.</p> </abstract>