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

Abstract

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 ^Aγ^T 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 ^Aγ^T chain with an additional mutation so far described and the third characterized by gene sequencing.

• Hb F‐Porto Torres
• γ‐Globin
• ^Aγ^T Globin