Further Characterization of Hb Bronovo [α103(G10)His→Leu; HBA2: c.311A>T] and First Report of the Homozygous State

Hemoglobin. 2020 May;44(3):174-178. doi: 10.1080/03630269.2020.1776322. Epub 2020 Jun 18.

Abstract

Hb Bronovo [α103(G10)His→Leu, HBA2: c.311A>T] is an α-globin variant that interferes with and decreases binding efficiency to α hemoglobin (Hb) stabilizing protein (AHSP), a chaperone molecule. The histidine residue at position 103 is integral to the AHSP hydrogen bond formation where disruption results in an increased quantity of cytotoxic free α-globin chains, thereby creating a similar pathophysiology as β-thalassemia (β-thal). We report a family with Hb Bronovo, including a homozygous proband, which resulted from maternal uniparental disomy (UPD). Although not detected by routine studies in previous reports, the variant protein is visible by intact mass spectrometry (MS).

Keywords: Hb Bronovo; microcytic anemia; thalassemia; α hemoglobin (Hb) stabilizing protein (AHSP); α-Globin.

Publication types

  • Case Reports

MeSH terms

  • Alleles*
  • Amino Acid Substitution
  • Child, Preschool
  • Chromosome Mapping
  • DNA Mutational Analysis
  • Female
  • Genetic Testing
  • Hemoglobins, Abnormal / genetics*
  • Heterozygote
  • Homozygote*
  • Humans
  • Inheritance Patterns
  • Male
  • Maternal Inheritance
  • Mutation*
  • Pedigree
  • alpha-Globins / genetics*
  • alpha-Thalassemia / diagnosis*
  • alpha-Thalassemia / genetics*

Substances

  • Hemoglobins, Abnormal
  • alpha-Globins
  • hemoglobin Bronovo