Genetic Analysis of β-Thalassemia Major and β-Thalassemia Intermedia in Brazil

Abstract

The development of methodologies to identify the molecular lesions responsible for different types of β-thalassemia has made it possible to correlate these data with clinical and hematological severity. We examined DNA from 35 patients with β-thalassemia, residents of the State of São Paulo, Brazil, for some types of genetic modifying factors: β-thalassemia mutations, the upstream Xmnl ^Gγ-globin gene polymorphisms, and α-globin gene deletions. Additionally, the β-like gene cluster haplotypes and the presence of the ^AY^T variant were studied. The following mutations were present in the 70 chromosomes studied: 54.3% codon 39 (C←T) (β^o); 18.6% IVS-I-6 (T←C) (β⁺); 18.6% IVS-I-110 (G←A) (β⁺), and 4.3% IVS-I-1 (G←T) (β^o). Haplotype II was associated with the nonsense mutation at codon 39, haplotype I with the IVS-I-110 and codon 39 mutations, and haplotypes VI and VII with the IVS-I-6 mutation. The Xmnl polymorphism was detected in three out of 31 patients studied. No α-thalassemia was detected among the thalassemia intermedia patients. The ^Aγ^T variant was present in 87.1% of 31 thalassemia patients and was associated with the codon 39/haplotype II and IVS-I-6/haplotype VI mutations. This is the first study of the Brazilian population that has analyzed the β-thalassemia mutations and other molecular variants, and has correlated them with the clinical manifestations.