HB Florida: A New Elongated C-Terminal β-Globin Variant Causing Dominant β-Thalassemia.

Abstract

An elongated C-terminal β-globin variant, due to the deletion of one nucleotide (-C) in between codons 140/141 (GCC/CTG→GCC/TG), which modified the C-terminal sequence and added 10 more residues to the β-chain [(141)Trp-Pro-Thr-Ser-Ile-Thr-Lys-Leu-Ala-Phe-Leu-Leu-Ser-Asn-Phe-(156)Tyr-COOH], was found in an 8-year-old Argentine girl of Spanish descent with clinical picture of β-thalassemia intermedia. The patient presented chronic moderate hemolytic anemia (RBC=3.8x10¹²/L, Hb=8.6 g/dL, Hct=28%), with pallor, jaundice and liver and spleen enlargement, having required blood transfusion for 5 times, during viral and bacterial infections; peripheral blood analysis revealed a remarkable degree of anisocytosis with microcytosis (RDW=28%, MCV=73.0 fl), poikilocytosis (with ovalocytes and schistocytes), hypochromia (MCH=22.6pg), 13% of reticulocytes and 2% of erythroblasts, punctate basophilia, elevated Hb A2 and Hb F levels (5% and 13%, respectively), without any detectable abnormal Hb (Hb and globin chain electrophoreses/HPLC). Tests for unstable hemoglobins were weakly positive, but the staining of the bone marrow cells with methyl violet allowed the visualization of many inclusion bodies, suggesting that this is probably a hyperunstable variant whose proteolysis in the bone marrow precursors results in dominant β-thalassemia phenotype, since the other β-locus showed no alteration. Mother's carrier was completely normal and the father, although not available for studying, was also probably normal.