Hemoglobinopathies in North Africa: A Review

Abstract

Hemolytic anemias are very common diseases. Among these diseases, hemoglobinopathies are widely spread throughout the Mediterranean Basin, including North Africa (Tunisia, Algeria and Morocco). Their severity and disabling nature make them a major public health problem. This study includes our data on the Tunisian hemoglobinopathies together with all the reports concerning epidemiological, clinical and molecular aspects in Algerian and Moroccan populations. Investigation methods begin with the application of several techniques for hemoglobin (Hb) analyses [electrophoresis and isoelectric focusing (IEF), micro-chromatography assay] of anemic patients in various hospital departments. Molecular investigation by DNA analyses completes the hematological and biochemical studies using polymerase chain reaction (PCR) followed by enzymatic digestion and/or denaturing gradient gel electrophoresis (DGGE), single strand conformation polymorphism (SSCP) and sequencing. These methods offer screening for a large number of families affected by sickle cell disease and thalassemia. In Tunisia, Algeria, and Morocco, more than 45 mutations have been identified on the β-globin gene. The most common in Tunisia and in Algeria are codon 39 (C>T) and IVS-I-110 (G>A), which together account for more than 50% of all mutations. In Morocco, the predominant mutations are codon 39 and frameshift codon (FSC) 8 (–AA). The identification of molecular defects in the βgene contributes to the development of diagnostic tests (prenatal diagnosis), and gives us the opportunity to help many couples. Our studies of the haplotypes of the β^S, codon 39 and IVS-I-110 origins allowed the hypothesis of a Benin origin for β^S, a local North African origin for codon 39 and an Eastern Mediterranean origin for IVS-I-110. The analysis of polymorphisms associated with a moderate phenotype of β-thalassemia (β-thal) and sickle cell disease in North Africa has shown, in several cases, a strong association with some mutations and restriction fragment length polymorphisms (RFLP) haplotype IX on the β-globin locus and the −158 (C>T) polymorphism in 5′ on the ^Gγ-globin gene. Finally, more knowledge on the regulation of the β-globin locus may contribute to the improvement of investigation, monitoring and treatment of hemoglobinopathies.

Keywords:

• Hemoglobinopathies
• Thalassemia
• Sickle cell disease
• Mutation
• Haplotype

ACKNOWLEDGMENTS

The authors express their thanks to CNRS, the TEMPRA (Région Rhône-Alpes and Gouvernorat de Monastir), MIRA, CMCU, and OHLL (Origine de l'Homme, des Langages et des Langues) programs for supporting the training of Amel Haj Khelil in France. The authors wish to thank Dr. Faouzi Baklouti, (Research Director) INSERM, CNRS, UMR 5534 at the Center of Molecular and Cellular Genetics in Lyon, France; Amel Haj Khelil studied “Cell differentiation and alternative splicing” in his laboratory. We thank the referee for his very helpful comments.

Declaration of Interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.