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.

We describe the molecular spectrum of a-thalassemia mutations in a population sample of newborns in the South-Iranian province of Hormozgan. Out of 660 randomly collected blood samples 218 (33%) had visibly elevated Hb Bart's. DNA was extracted from 78 samples out of this selection (n = 156), of which 114 alleles were found to carry an a-thalassemia defect. Besides the common -a 3.7 (79.1%), -a 4.2 (1.7%), and a -5nt a alleles (4.3%), three novel nondeletional a-thalassemia mutations were found; the a 2 cd19 (-G) frameshift mutation (12.2%), the a 1 IVS1-148(A?G) (0.9%) affecting the splice acceptor site consensus sequence and the cd14 (TGG?TAG) (0.9%), which creates a premature stop codon in the first exon of the a 1 -gene. A fourth mutation in the a 1 -gene, the IVS1-38 (C?T) (0.9%) of undetermined effect, was found in an individual heterozygous for the a 2 cd19(-G) mutation. Am.

The very high frequency of the Benin haplotype in our study suggests that the β(S) mutation present in Tunisia may have originated from the Benin region and was brought to Tunisia along the slave trade routes. However, another atypical haplotype observed a new emergence in our population and could be considered as specific to Tunisian chromosome β(S).