title: Maximal gamma-globin expression in the compound heterozygous state for -175G gamma HPFH and beta degree 39 nonsense thalassaemia: a case study.
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.
authors.affiliation: Istituto CNR per lo Studio della Patologia del Sangue e degli Organi Emopoietici, Sassari, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Pistidda
authors.forename: L
authors.initials: L
authors.lastname: Frogheri
authors.forename: L
authors.initials: L
authors.lastname: Guiso
authors.forename: L
authors.initials: L
authors.lastname: Manca
authors.forename: F
authors.initials: F
authors.lastname: Dore
authors.forename: L
authors.initials: L
authors.lastname: Mura
authors.forename: M
authors.initials: M
authors.lastname: Longinotti
mesh_terms: D000328:Adult; D005192:Family Health; D005319:Fetal Hemoglobin / Q000737:chemistry / Q000235:genetics*; D015870:Gene Expression; D006453:Hemoglobinopathies / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D009154:Mutation; D015995:Prevalence; D017086:beta-Thalassemia / Q000453:epidemiology / Q000235:genetics*; D005719:gamma-Globulins / Q000737:chemistry / Q000235:genetics*
chemical_list: D005719:gamma-Globulins; D005319:Fetal Hemoglobin