MOLECULAR SPECTRUM OF<i>α</i>-THALASSEMIA IN TUNISIA: EPIDEMIOLOGY AND DETECTION AT BIRTH

Abstract

We present the characterization of the molecular spectrum and frequency data of alpha-thal (thal) defects in Tunisia, and an evaluation of the efficacy and limitations of Hb Bart's (gamma4) measurement for the screening of alpha-thal at birth. Cord blood samples were collected from two different areas: the northeast of the country, an area where Hb H (beta4) 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 alpha-thal defects and nondeletional mutations were screened. In the northeastern samples, selected for the presence of Hb Bart's and microcytosis, the -alpha3.7 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 -alpha4.2 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 alpha-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 alpha2 gene and the African polymorphism in the second intron of the same gene, were found in 3.5% of the alleles. No alpha0-thal alleles were found among the 304 blood samples studied at the DNA level during this survey.