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

Abstract

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.

A First Report of Hb Alesha [β67(E11)Val>Met, GTG>ATG] in an Iranian Patient

“…According to this study and the previous analysis [ 1 - 3 , 6 , 7 , 8 ] that were carried out on the Hb Alesha-Bristol, it has been confirmed that this mutation is always caused as a result of a de novo mutation. It has also been reported in subjects of different origins, three from Japan, two from Russia, as well as one from each of German, Argentina, Brazil, China, and Britain, suggesting that this mutation is not dependent on especial origins [ 7 , 9 ] . Moreover, the similar mutation has been reported in α-globin chain (α62(E11) Val to Met, i.e.…”

Case report: Curing a rare, unstable hemoglobin variant Hb Bristol-Alesha using haploidentical hematopoietic stem cell transplantation

“…The Met residue is subsequently modified to Asp, probably via oxidative mechanisms (10). To the best of our knowledge, only 15 cases of this variant have been reported, all of which were dependent on blood transfusion (Table 1) (8,(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). According to this case and a previous analysis conducted on Hb Bristol-Alesha, it is always caused by de novo mutations.…”