title: Molecular spectrum of alpha-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.
authors.affiliation: Hemoglobinopathies Group, Laboratory of Hematology, Pasteur Institute of Tunis, 1002 Tunis le Belvedere, Tunisia.
authors.forename: Amine
authors.initials: A
authors.lastname: Zorai
authors.forename: Cornelis L
authors.initials: CL
authors.lastname: Harteveld
authors.forename: Achech
authors.initials: A
authors.lastname: Bakir
authors.forename: Peter
authors.initials: P
authors.lastname: Van Delft
authors.forename: Abdelaziz
authors.initials: A
authors.lastname: Falfoul
authors.forename: Koussay
authors.initials: K
authors.lastname: Dellagi
authors.forename: Salem
authors.initials: S
authors.lastname: Abbes
authors.forename: Piero C
authors.initials: PC
authors.lastname: Giordano
mesh_terms: D004247:DNA / Q000097:blood / Q000235:genetics; D004909:Erythrocyte Indices / Q000235:genetics; D004913:Erythrocytes, Abnormal / Q000737:chemistry / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology; D006580:Genetic Carrier Screening / Q000379:methods; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D006455:Hemoglobins, Abnormal / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D015997:Neonatal Screening / Q000379:methods*; D011110:Polymorphism, Genetic / Q000235:genetics; D014416:Tunisia / Q000453:epidemiology; D017085:alpha-Thalassemia / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology* / Q000235:genetics
chemical_list: D006455:Hemoglobins, Abnormal; D004247:DNA; C030448:hemoglobin Bart's