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Hb Bristol-Alesha [HBB: c.202G>A; β 67 Val>Met] is a rare structural variant of hemoglobin (Hb) resulting from a GTG>ATG substitution at codon 67 of the β-globin gene that leads to the replacement of valine by methionine in the corresponding position of the β-globin chain. The methionine residue is subsequently modified to aspartic acid [β67(E11)Val-Met→Asp], possibly by autoxidation mechanisms. This substitution prevents normal non-polar binding of Val67 to the heme group, resulting in molecular instability and severe hemolysis. We identified Hb Bristol-Alesha (in the heterozygous state), as the cause of severe congenital hemolytic anemia in an 11-month-old girl of mixed (native Indian and European) ethnic origin from the Midwestern region of Brazil, whose parents were clinically and hematologically normal. The mutation on the β-globin gene was found to have been coinherited with the α212 patchwork allele.

Three novel α-globin variants were found during a screening program for hemoglobinopathies in blood donors at the UNICAMP Hematology and Hemotherapy Center, Campinas, State of Sao Paulo, Southeastern Brazil. They were named for the town of origin of the carrier as Hb Itapira [α30(B11)Glu→Val], Hb Bom Jesus da Lapa [α30(B11)Glu→Ala] and Hb Boa Esperanca [α16(A14)Lys→Thr]. Hb Itapira, like Hb Bom Jesus da Lapa, shows an electrophoretic mobility similar to that of Hb S [β6(A3)Glu→Val, GAG→GTG] at alkaline pH; it is associated with a triplicate α-globin allele (αααanti 3.7) and corresponds to only 5.5% of the total hemoglobin (Hb). Hb Boa Esperanca, found in two different individuals, moves faster than Hb A and exhibits an abnormal functional performance.

Analysis of DNA polymorphic sites is an important tool for the detection of gene flow in human evolutionary studies and to study the genetic background for gene mutations. The β-globin locus contains several single-base restriction fragment length polymorphism (RFLP) sites throughout chromosome 11. In addition to these polymorphic sequence repeats, others are being studied in order to expand our knowledge concerning the role between haplotype-genotype and phenotype associations. Far downstream of the expressed β-globin genes, there is a hypersensitive site (HS) whose function remains obscure. We sequenced this region in 27 thalassemia patients and found a new pattern in the micro-satellite-like AT-rich region of this site: a new TAA insertion in addition to the one previously described in sickle cell patients with a concomitant polymorphism (G→A). This new variation was found to be linked to the IVS-I-6 (T→C) mutation. This polymorphism may be useful for studies concerning genotype and phenotype associations.

A novel hemoglobin (Hb) variant was found during a screening program for hemoglobinopathies in blood donors at the Hematology Center of the State University of Campinas, Campinas, Brazil. The carri...