MOLECULAR SPECTRUM OF α-THALASSEMIA IN TUNISIA: EPIDEMIOLOGY AND DETECTION AT BIRTH

Abstract

We present the characterization of the molecular spectrum and frequency data of α-thal (thal) defects in Tunisia, and an evaluation of the efficacy and limitations of Hb Bart's (γ4) measurement for the screening of α-thal at birth. Cord blood samples were collected from two different areas: the northeast of the country, an area where Hb H (β4) disease frequently occurs, and Tunis, the capital city, representative of the average Tunisian population. From the first group, 110 samples with Hb Bart's and/or microcytosis at birth were selected from 1270 randomly collected samples. Two additional population samples, one from the same northeastern region (n=90), the other from Tunis (n=104) were collected randomly. Nine common deletional α-thal defects and nondeletional mutations were screened. In the northeastern samples, selected for the presence of Hb Bart's and microcytosis, the −α3.7 deletion was the most common defect (4.5% allele frequency) followed by a polyadenylation (poly A) signal mutation (1.8%), the five nucleotide (nt) deletion and the −α4.2 deletion (both 0.9%). The African polymorphism (G→TCGGCCC at position 7238 and T→G at 7174) was found with an allele frequency of 11% in the selected northeastern samples. In the random population samples, the overall α-thal allele frequency was 4% in the northeast region, against 2% in the average Tunisian population. The +14 (G→C) polymorphism in the 5′UTR (untranslated region) of the α2 gene and the African polymorphism in the second intron of the same gene, were found in 3.5% of the alleles. No α0-thal alleles were found among the 304 blood samples studied at the DNA level during this survey.