Rare hemoglobin variants in Tunisian population

Area of Science:

• Hematology
• Genetics
• Molecular Biology

Background:

• Hemoglobinopathies are prevalent in Tunisia, with numerous thalassemic alleles identified in beta-globin and alpha-globin genes.
• Beyond common variants like Hb S, C, and O-arab, unusual hemoglobin variants have been detected in the Tunisian population.

Purpose of the Study:

• To phenotypically and molecularly characterize eight Tunisian subjects with hemoglobin variants.
• To provide an updated review of hemoglobin variants identified in Tunisia, emphasizing rare and uncommon types.

Main Methods:

• Hematological indices and hemoglobin patterns analyzed using alkaline electrophoresis and isoelectric focusing (IEF).
• Hemoglobin fractions quantified by cation exchange High-Performance Liquid Chromatography (HPLC).
• Genomic analysis involved Polymerase Chain Reaction (PCR) amplification of coding regions followed by dye terminator sequencing.

Main Results:

• Seven previously undescribed hemoglobin variants were identified in the Tunisian subjects.
• A novel delta-chain variant, HbA2-Tunis [δ46(CD5), Gly → Glu, GGG → GAG], was characterized.
• Twenty-one rare hemoglobin variants affecting alpha, delta, gamma, and beta-globin genes were identified, with some leading to severe phenotypes.

Conclusions:

• The study identified a significant number of rare hemoglobin variants in Tunisia, including novel and uncommon types.
• The ethnic history of Tunisia likely contributes to the observed high variability of rare hemoglobin variants.
• These findings underscore the importance of comprehensive hemoglobin variant screening in the Tunisian population.