Hb F-Porto Torres [Aγ75(E19)Ile→Thr, 136(H14)Ala→Ser]: A Novel Variant of the Aγ Chain Having Two Substitutions, One Being that of Hb F-Sardinia

• Published in: Hemoglobin 2004, Vol.28 (4), p.297-303
• Main Authors: Pirastru, Monica, Manca, Laura, Palici di Suni, Marcella, Speziga, Silvia Maria, Masala, Bruno
• Format: Article
• Language: English
• Subjects: Globin; Hb F-Porto Torres; γ-Globin
• ISSN: 0363-0269; 1532-432X
• DOI: 10.1081/HEM-200038868

The abnormal Hb F-Porto Torres [Aγ75(E19)Ile→Thr, 136(H14)Ala→Ser] was observed during a cord blood survey for hemoglobinopathies in North Sardinia. This silent variant showed the same mobility as Hb F-Sardinia in isoelectric focusing (IEF) of the tetramers, whereas the abnormal globin chain was clearly separated by acid-urea-Triton polyacrylamide gel electrophoresis (AUT-PAGE) from the normal Gγ- and Aγ-globin chains. Separation of the globin chains by reversed phase high performance liquid chromatography (HPLC) indicated the following percentages: Gγ 68.4, Aγ 14.0, Xγ 17.6, that strongly suggested the abnormal chain as being a variant of the Aγ-globin. Sequencing of the γ-globin genes indicated that the mutated gene was in fact an Aγ with two nucleotide replacements, one being the ATA→ACA (Ile→Thr) at codon 75 (the so-called AγT of the rather common Hb F-Sardinia) and the second the GCA→TCA (Ala→Ser) at codon 136. This new variant is the seventh having the sequence of the AγT chain with an additional mutation so far described and the third characterized by gene sequencing.