A different molecular pattern of beta-thalassemia mutations in northeast Brazil

Abstract

The main hereditary hemoglobin (Hb) disorders of clinical significance in Brazil are sickle cell disease and beta-thalassemia (thal). The sickle gene was introduced by the slave trade, whereas beta-thal was introduced later, due to a massive immigration (mostly by Italians) between 1870 and 1953, mainly to the southeast region of Brazil. Molecular studies performed in the southeast of the country showed a marked prevalence of the nonsense mutation at codon 39 (C --> T) (47-54%), leading to severe forms of beta0-thal. However, the northeast region of the country has a different demographic history, characterized by the absence of the massive Italian immigration. Owing to this and since the majority of cases of beta-thal in Pernambuco, a state located in the northeast of the country, have mild or intermediate clinical and laboratory features, we would predict a different spectrum of beta-thal mutations in this region. We examined 60 unrelated patients (86 beta-thal chromosomes) under regular clinical follow-up in Pernambuco: 6 were regularly transfused beta-thal major subjects, 20 had beta-thal intermedia, 20 had Hb S/beta-thal and 14 were beta-thal trait individuals. The following mutations were found: IVS-I-6 (T --> C) 62.8%, IVS-I-1 (G -->A) 15.1%, IVS-I-5 (G --> C) 9.3%, IVS-I-110 (G --> A) 8.2%, codon 39 (C --> T) 3.5%, and codon 30 (AGG --> AGC) 1.1%. These data show different patterns of beta-thal mutations in two regions of Brazil, demonstrating a thus far unrevealed heterogeneity of the disease in the country.