Mutation Spectrum of Hemoglobinopathies in Tunisia

Hemoglobinopathies are the most prevalent recessive disorders worldwide, characterized by wide molecular and clinical heterogeneity. They result from mutations within the alpha-, beta-, or delta-globin gene leading to aberrant expression or protein function. These abnormalities are widely spread throughout the Mediterranean basin. Due to their severity and disabling nature, hemoglobinopathies represent a major public health problem. Mutational screening of abnormal hemoglobins (Hbs) allows the creation of a mutation map, which forms the basis for a potential national prevention program in Tunisia.

A total of 260 Tunisian subjects were investigated using biochemical and molecular analyses to identify defects in the globin genes (HBA, HBB, and HBD). The study is aimed at determining the molecular spectrum of hemoglobinopathies and contributing to the development of a comprehensive Hb mutation map in Tunisia.

Twenty-one β-thalassemia mutations and 16 rare Hb variants were reported, affecting the HBA, HBD, and HBB genes. Rare Hb variants were identified and described for the first time among Tunisian patients, including Hb A₂-Babinga (HBD:c.410G>A; delta 136: Gly → Asp, GGT → GAT). Other variants, such as Hb Knossos, Hb Summer Hill, Hb Hope, and Hb Köln, which are uncommon in the Mediterranean region, were also detected.

This study provides an updated overview of β-thalassemia mutations and rare Hb variants in the Tunisian population. These findings are essential for understanding genetic and clinical diversity, improving the clinical management of hemoglobinopathies, and enhancing public health initiatives.