Hb Monza: A novel extensive HBB duplication with preserved α-β subunit interaction and unstable hemoglobin phenotype

Unstable hemoglobins are abnormal forms of hemoglobin that can cause acute hemolytic crises, a condition where many red blood cells are destroyed. This typically results from small changes in the β hemoglobin subunit gene (HBB). Researchers at the University of Milan-Bicocca have discovered a new variant, hemoglobin Monza, which, despite being linked to instability, is caused by a long duplication in HBB. Using 3D computational modeling, the study explains how hemoglobin Monza remains stable under normal conditions and why it becomes unstable during stress such as fever. The research also shows that ⍺-β subunit interactions can be maintained even with extreme duplications of the HBB gene and highlights the value of modern protein modeling tools for studying complex cases with unknown variants.