Molecular Heterogeneity of β-Thalassemia in Algeria: How to Face Up to a Major Health Problem

Abstract

This study concerns the molecular characterization of β-thalassemia (β-thal) alleles in 210 chromosomes. In the studied population, mutations were detected in 98% of the β-thalassemic chromosomes. Twenty-one molecular defects have been found, where the five dominant mutations, IVS-I-110 (G>A), nonsense mutation at codon 39 (C>T), the frameshift codon (FSC) 6 (−A), IVS-I-1 (G>A), and IVS-I-6 (T>C), account for 80% of the independent chromosomes. Among the remaining alleles, 16 different mutations were identified, half of them being described for the first time in Algeria. These include the −101 (C>T) and the −90 (C>T) mutations in the distal and proximal promoter elements, respectively, the FSC 8 (−AA), IVS-I-5 (G>T), IVS-I-128 (T>G), FSC 47 (+A), IVS-II-1 (G>A), and the substitution in the polyadenylation signal (poly A) site AATAAA>AATGAA. Haplotype analyses on rare variants were performed. The possible origin of these mutations either by founder effect or by migrations is discussed, and raises the question of an adequate strategy to be used adapted to socio-economical status.

Keywords:

• β-Thalassemia (β-thal)
• Diagnosis strategy
• Genetic heterogeneity