Coinheritance of Hb Bristol-Alesha [β67(E11)Val→Met; HBB: c.202G>A] and the α212 Patchwork Allele in a Brazilian Child with Severe Congenital Hemolytic Anemia

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.