The Spectrum of β-Thalassemia Mutations in a Population from the Brazilian Amazon.

The spectrum of β-thalassemia (β-thal) mutations was investigated for the first time in a cohort of 33 unrelated patients from the Brazilian Amazon attending the Center for Hemotherapy and Hematology of the Pará Foundation (HEMOPA), in Belém, the state capital of Pará, Northern Brazil. Identification of the β-thal mutations was made by direct genomic sequencing of the β-globin gene. Mutations were identified in all patients, corresponding to a spectrum of 10 different point mutations and a total of 37 alleles studied. HBB: c.92 + 5G > A [IVS-I-5 (G > A)], was the most common β-thal mutation, followed by HBB: c.118C > T [codon 39 (C > T)], HBB: c.-138C > T [-88 (C>T)], HBB: c.92 + 1G > A [IVS-I-1 (G > A)] and HBB: c.92 + 6T > C [IVS-I-6 (T > C)] mutations. These five mutations (four Mediterranean origin and one African origin) accounted for 86.5% of the β-thal alleles. The profile of β-thal mutations found in northern Brazil is different from those described in other regions of the country. In the southeast and south, the nonsense mutation HBB: c.118C > T is the most prevalent, followed by HBB: c.93-21G > A [IVS-I-110 (G > A)], whereas in the northeast, HBB: c.92 + 6T > C has been identified as the most common mutation, followed by HBB: c.92 + 1G > A. This heterogeneous geographical distribution is certainly related to the ancestry of Brazilian populations because they have similar genetic backgrounds (European, African and Amerindian), although with slightly different admixture proportions. Furthermore, the European contribution in the southeast and south was largely made up of immigrants of other nationalities, such as Italian and Spanish, in addition to Portuguese.