Pedroso Gisele A, Kimura Elza M, Santos Magnun N N, Albuquerque Dulcinéia M, Ferruzzi Jucilane L H, Jorge Susan E, Costa Fernando F, Saad Sara T O, Sonati Maria F
a Hemoglobinopathies Laboratory, Department of Clinical Pathology , School of Medical Sciences, State University of Campinas (UNICAMP), Campinas , São Paulo , Brazil.
b Hematology and Hemotherapy Center, State University of Campinas (UNICAMP), Campinas , São Paulo , Brazil.
Hemoglobin. 2017 May;41(3):203-208. doi: 10.1080/03630269.2017.1340305. Epub 2017 Jul 3.
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.
血红蛋白布里斯托尔 - 阿莱莎[HBB: c.202G>A; β67缬氨酸>甲硫氨酸]是一种罕见的血红蛋白（Hb）结构变异体，由β - 珠蛋白基因第67密码子处的GTG>ATG替换引起，导致β - 珠蛋白链相应位置的缬氨酸被甲硫氨酸取代。随后，甲硫氨酸残基可能通过自氧化机制被修饰为天冬氨酸[β67(E11)缬氨酸 - 甲硫氨酸→天冬氨酸]。这种替换阻止了缬氨酸67与血红素基团的正常非极性结合，导致分子不稳定和严重溶血。我们在一名来自巴西中西部地区、具有（印度本土和欧洲）混合种族血统的11个月大女孩中，鉴定出血红蛋白布里斯托尔 - 阿莱莎（杂合状态）是严重先天性溶血性贫血的病因，其父母在临床和血液学方面均正常。发现β - 珠蛋白基因上的突变与α212拼接等位基因共同遗传。
