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

The abnormal Hb F-Porto Torres [ Ag75(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 Gg- and Ag-globin chains. Separation of the globin chains by reversed phase high performance liquid chromatography (HPLC) indicated the following percentages: Gg 68.4, Ag 14.0, Xg 17.6, that strongly suggested the abnormal chain as being a variant of the Ag-globin. Sequencing of the g-globin genes indicated that the mutated gene was in fact an Ag with two nucleotide replacements, one being the ATA!ACA (Ile!Thr)at codon 75 (the so-called AgT 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 AgT chain with an additional mutation so far described and the third characterized by gene sequencing.