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.

Keywords:

• α212 Patchwork allele
• Brazilian population
• congenital hemolytic anemia
• Hb Bristol-Alesha
• unstable Hb variant

Acknowledgments

The authors would like to thank Dr. Carolina Lanaro and Daniela P. Leonardo at the Hematology and Hemotherapy Center, State University of Campinas, Campinas, São Paulo, Brazil, for their help with the DNA cloning and sequencing procedures and Ana Paula M. Geraldo at the Integrated Center for Pediatric Hematology/Oncology Research (CIPOI), State University of Campinas, Campinas, São Paulo, Brazil, for performing the IEF analyses. We complied with the ethical principles for medical research involving human subjects World Medical Association (WMA) Helsinki Declaration.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This study received financial support from the State of São Paulo Research Foundation (FAPESP) [grant no. 2014/00984-3; fellowship no. 2015/13710-1].