Hb Bronte or α93(FG5)Val→Gly: A New Unstable Variant of the α2‐Globin Gene, Associated with a Mild α⁺‐Thalassemia Phenotype

Abstract

We report a new unstable variant identified in three carriers of a family from East Sicily; it was named Hb Bronte after the place from which the family originated. DNA sequencing from nucleotides −181 to +894 (α1) and to +884 (α2) revealed a GTG→GGG substitution at codon 93 of the α2‐globin gene. The MCV and MCH values were at the lower end of the normal range in the carriers. On cation exchange high performance liquid chromatography (HPLC), the Hb A₂ level was apparently increased to around 6%, and a small abnormal peak (0.3–0.4%) was detected after Hb A₂. Two abnormal bands were detected by cellulose acetate electrophoresis: a major band (about 3–4%) migrated between Hb A and Hb F; a minor band (<1%) migrated between Hb A₂ and carbonic anhydrase. Normal values of Hb A₂ were detected by DEAE microchromatography. On reversed phase HPLC the variant chain was not detected, and most likely it was eluted with the α chain peak. The isopropanol stability test was very slightly positive in the carriers. Hemolytic symptoms were absent with the exception of indirect bilirubin, which was at high borderline in 2/3 carriers. In biosynthesis in vitro, the specific activity of the α chains was much higher than that of the β‐globin chains, and the α/β biosynthetic ratio in the mother and proband was of the β‐thalassemia (thal) type (2.24 and 2.54, respectively). Time course experiments showed that the increase of the ³H‐specific activity of the peak containing normal and variant α chains was not linear and was much higher than that of β chains; moreover, the α/β biosynthetic ratio varied during the 2 hours incubation.

• α⁺‐Thalassemia (thal)
• Unstable hemoglobin (Hb) variants
• Globin chain biosynthesis
• In vitro
• α‐Globin gene disorders