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The variant fetal hemoglobin F Texas I is abnormally acetylated

A S Keitt1, R T Jones

  • 1Department of Pathology, University of Florida College of Medicine, Gainesville 32610.

American Journal of Hematology
|May 1, 1988
PubMed

Insights

This study identifies a novel fetal hemoglobin variant, Hb F Texas I, in infants. This variant exhibits increased N-alpha-acetylation, a previously undocumented phenomenon in abnormal fetal hemoglobins.

Area of Science:

  • Hematology
  • Biochemistry
  • Genetics

Background:

  • Fetal hemoglobin (HbF) plays a crucial role in oxygen transport during gestation.
  • Hemoglobin variants can arise from genetic mutations, potentially affecting oxygen-carrying capacity and stability.
  • Electrophoretic screening of cord blood is a standard method for detecting hemoglobinopathies.

Purpose of the Study:

  • To characterize a novel hemoglobin variant detected in infants.
  • To elucidate the molecular basis and post-translational modifications of this variant.
  • To investigate the acetylation status of the identified abnormal fetal hemoglobin.

Main Methods:

  • Electrophoretic cord blood screening
  • Isoelectric focusing (IEF)
  • Anion exchange chromatography (AEC)
  • High-performance liquid chromatography (HPLC)
  • Tryptic hydrolysis and peptide analysis
  • Edman degradation
  • Fast atom bombardment mass spectrometry (FABMS)

Main Results:

  • A novel fetal hemoglobin variant, Hb F Texas I, was identified in two related infants.
  • Structural analysis revealed a glu----lys substitution at position 5 in the A gamma T-1 peptide.
  • A minor fraction of Hb F Texas I chains showed resistance to Edman degradation, indicating acetylation.
  • FABMS confirmed N-alpha-acetylation of the variant, with acetylation levels nearly three times higher than normal HbF.
  • This increased acetylation was stable over a year in the proband.

Conclusions:

  • Hb F Texas I is a novel variant of fetal hemoglobin characterized by a specific amino acid substitution.
  • This variant exhibits significantly increased N-alpha-acetylation, a novel finding for abnormal fetal hemoglobins.
  • The increased acetylation may represent a compensatory mechanism or a unique characteristic of this hemoglobinopathy.

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