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

Abstract

This study concerns the molecular characterization of beta-thalassemia (beta-thal) alleles in 210 chromosomes. In the studied population, mutations were detected in 98% of the beta-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.

Presence of the IVS-I-6-Mutated Allele in Beta-Thalassemia Major Patients Correlates with Extramedullary Hematopoiesis Incidence

“…The IVS-I-6 (T→C) mutation is one of the most common causes of β-thalassemia among individuals of Mediterranean and Middle Eastern ancestry [39,40]. Its high incidence has been reported among populations from Portugal [41]; Spain [42,43]; Albania [44]; the region of former Yugoslavia [45,46,47,48]; Greece [49,50,51,52]; Algeria [53]; Egypt [54]; Palestine [55,56]; Lebanon [57]; Syria [58,59]; Cyprus [60]; Turkey [61,62,63,64,65]; Saudi Arabia [66,67]; Iraq [68,69,70,71]; Iran [72,73,74]; and elsewhere. It results from a base substitution close to the 5′ splice junction, between exon I and intron I, and within a conserved consensus sequence, interfering with mRNA splicing and, consequently, reducing its efficiency.…”

Compound heterozygosity of a silent beta‐thalassemia mutation at the 3′‐untranslated region (HBB: c.*132 C>T) and beta‐zero thalassemia results in thalassemia intermedia

“…Mutations in the region are generally associated with silent beta‐thalassemia with no hematologic abnormalities detected in carriers. Mutations in 3′‐UTR are rather uncommon with 18 reported mutations to date …”

Prevalence of β-Thalassemia and Hemoglobin E in Two Migrant Populations of Manipur, North East India

“…The -90 C/T mutation is a rare and transcriptional b-thalassemia mutation that was first reported among the Portugese (0.97%) by Faustino et al (1992). It was also reported among the Algerian population (Boudrahem-Addour et al, 2009), Jamaican population (Donaldson et al, 2000), Chinese population ( Jia et al, 2003;Tan et al, 2003), and Indian population (Ramachandran et al, 2003;Gorakshakar et al, 2005;Sinha et al, 2009).…”