Maximal gamma-globin expression in the compound heterozygous state for -175G gamma HPFH and beta degree 39 nonsense thalassaemia: a case study

Eur J Haematol. 1997 May;58(5):320-5.

Abstract

The -175 (T-->C) G gamma hereditary persistence of fetal haemoglobin is a very rare promoter mutation occurring in Caucasians as well as in African-Americans. Heterozygotes for this non-deletional HPFH show 20% HbF, mostly of G gamma type. We describe here a healthy Sardinian man who coinherited -175 (T-->C) G gamma HPFH with the beta-thalassaemia codon 39 nonsense mutation in trans; he showed 64% HbF, 100% of G gamma type. Although the beta-globin haplotype pattern (II/II) was indicative of the presence of the A gamma T allele on both chromosomes, the A gamma T expression was undetectable by HPLC even in red cell populations separated by age. The proband was, moreover, homozygous for the -4 bp deletion at position -225 to -222 of A gamma promoter which has recently been associated with decreased A gamma T globin expression. These findings suggest that this maximal overexpression of G gamma-globin probably reflects intensified stimulation of the mutated G gamma promoter in this hitherto undescribed genetic condition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Family Health
  • Fetal Hemoglobin / chemistry
  • Fetal Hemoglobin / genetics*
  • Gene Expression
  • Hemoglobinopathies / genetics*
  • Heterozygote
  • Humans
  • Italy / epidemiology
  • Male
  • Mutation
  • Prevalence
  • beta-Thalassemia / epidemiology
  • beta-Thalassemia / genetics*
  • gamma-Globulins / chemistry
  • gamma-Globulins / genetics*

Substances

  • gamma-Globulins
  • Fetal Hemoglobin