Hb Wroclaw (HBA1: c.266C>A) Detected by Capillary Electrophoresis Co-Inherited with Hb Icaria (HBA2: c.427T>A) Produces Erythrocytosis in an Italian Male - Abstract
Objectives: To date, more than 600 different ?-globin gene defects, structural variants, and thalassemias have been described [1]. Thalassemias are mainly produced by greater or lesser extensive deletions or, more rarely, point defects. A variety of phenotypes can be observed when several thalassemia defects are inherited in combination with numerous Hb variants. Methods: A 22-year-old man from Crotone (Calabria, Italy) with significant erythrocytosis was examined for hemoglobin (Hb) defects by capillary electrophoresis (CE). Molecular characterization was performed by direct sequencing of HBA1 and HBA2 genes and by multiple ligation-dependent probe amplification (MLPA) to detect deletions/duplications within the ?-gene cluster. Results: Two abnormal peaks were observed by CE: a main one in anodal position with respect to Hb A and a secondary one in anodal position with respect to Hb A2. Direct sequencing of HBA1 and HBA2 genes showed the presence of two point mutations respectively: HBA1: c.266C>A (Hb Wroclaw) and HBA2: c.427T>A (Hb Icaria, thalassemic variant).
Conclusions: Hb Wroclaw is a rare variant reported in HbVar in 2008 but not described in the literature. The mutation at position F9, codon 88 of the amino acid alanine (Ala), leads to substitution with glutamic acid (Glu). This mutation results in a structural change in the ?-globin chain and, in the presence of Hb Icaria, produces a relative increase in Hb Wroclaw, this causes significant erythrocytosis in the proband and mother.