GENETIC-ANALYSIS OF BETA-THALASSEMIA MAJOR AND BETA-THALASSEMIA-INTERMEDIA IN BRAZIL

The development of methodologies to identify the molecular lesions res ponsible for different types of beta-thalassemia has made it possible to correlate these data with clinical and hematological severity. We e xamined DNA from 35 patients with beta-thalassemia, residents of the S tate of Sao Paulo, Brazil, for some types of genetic modifying factors : beta-thalassemia mutations, the upstream XmnI (G)y-globin gene polym orphisms, and alpha-globin gene deletions. Additionally, the beta-like gene cluster haplotypes and the presence of the Y-A(T) variant were s tudied. The following mutations were present in the 70 chromosomes stu died: 54.3% codon 39 (C-->T) (beta degrees); 18.6% IVS-I-6 (T-->C (bet a(')); 18.6% IVS-I-110 (G-->A) (beta+), and 4.3% IVS-I-1 (G-->T) (beta degrees). Haplotype II was associated with the nonsense mutation at c odon 39, haplotype I with the IVS-I-110 and codon 39 mutations, and ha plotypes VI and VII with the IVS-I-6 mutation. The XmnI polymorphism w as detected in three out of 31 patients studied. No alpha-thalassemia was detected among the thalassemia intermedia patients. The Y-A(T) var iant was present in 87.1% of 31 thalassemia patients and was associate d with the codon 39/haplotype II and IVS-I-6/haplotype VI mutations. T his is the first study of the Brazilian population that has analyzed t he beta-thalassemia mutations and of her molecular variants, and has c orrelated them with the clinical manifestations.