BETA-THALASSEMIA, HB S-BETA-THALASSEMIA AND SICKLE-CELL-ANEMIA AMONG TUNISIANS

We analyzed the mutations present in 19 patients with beta-thalassemia major, in 11 patients with Hb S-beta-thalassemia, and the beta-S haplotypes of 34 patients with sickle cell anemia. The study included 84 relatives. Dot-blot analysis of amplified DNA with various specific oligonucleotide probes identified 11 different known beta-thalassemia mutations and frameshifts; a new frameshift at codons 25/26 (+T) was detected through sequencing of amplified DNA. The common beta-thalassemia mutations at codon 39 (C --> T) and at IVS-I-110 (G --> A) were also most prevalent among the Tunisian patients, while the milder T --> C mutation at IVS-I-6 was not found. All mutations cause a beta-degrees-thalassemia or a severe beta+-thalassemia [T --> A at -30; IVS-I-5 (G --> A); IVS-I-110 (G --> A)] which explains the need for regular blood transfusions in the thalassemia major and S-beta-thalassemia patients. Nearly all sickle cell anemia patients carried the beta-S mutation on a chromosome with haplotype 19 (or Benin) and all had severe anemia with sickling complications. Identification of the beta-S haplotype was through dot-blot analysis with oligonucleotide probes that detect mutations in the G-gamma and A-gamma promoter sequences, specific for this haplotype.