Hb Cardarelli [β86(F2)Ala→Pro]: A New Unstable and Hyperaffine Variant in Association with β⁺‐Thalassemia

Abstract

Hb Cardarelli [β86(F2)Ala→Pro] is a new unstable and high oxygen affinity variant found in several members of a family from Naples, Southern Italy. A detailed structural and functional characterization of the variant was performed on two subjects, at both the protein and DNA level. The first patient exhibited 43% of the variant hemoglobin (Hb) without major hematological problems. The proband showed 82% of the abnormal Hb in association with β⁺‐thalassemia (thal) that caused relevant erythrocytosis requiring frequent phlebotomies. Structural investigation of the Hb variant by mass spectrometric methodologies identified the amino acid replacement as Ala→Pro at β86. The corresponding DNA mutation GCC→CCC at codon 86 of the β‐globin gene was assessed by both DNA sequencing and amplification refractory mutation system (ARMS) techniques. Functional studies carried out on whole blood and diluted hemolysates from both patients demonstrated increased oxygen affinity, decreased Bohr effect, reduced heme–heme interaction and nearly halved 2,3‐diphosphoglycerate (2,3‐DPG) and chloride effects.

• Variant hemoglobin (Hb)
• Erythrocytosis
• High affinity
• Mass spectrometry