title: Molecular, haematological and clinical studies of the -101 C --> T substitution of the beta-globin gene promoter in 25 beta-thalassaemia intermedia patients and 45 heterozygotes.
abstract: We report the clinical, haematological, biosynthetic and molecular data of 25 double heterozygote beta-thalassaemia intermedia patients and 45 beta-thalassaemia heterozygotes with the C --> T substitution at nucleotide position -101 from the Cap site, in the distal CACCC box of the beta-globin gene promoter. This mutation is considered the most common amongst the silent beta-thalassaemia mutations in Mediterranean populations. Of the 25 compound heterozygotes for the beta -101 C --> T and common severe beta-thalassaemia mutations, all but one had mild thalassaemia intermedia preserving haemoglobin levels around 9.5 g/dl and haemoglobin F levels < 25%. The only transfused patient was characterized to have an additional alpha-globin gene. Strict assessment of haematological and biosynthetic findings in the heterozygotes for the beta -101 C --> T mutation (excluding six cases with an alpha-globin gene defect) demonstrated that less than half of them had completely normal (silent) haematology; the remainder had either high haemoglobin A2 values (in the range of 3.7-5.1%) and/or low red cells indices and/or raised haemoglobin F values. The alpha/non-alpha-globin chain synthesis ratios were generally raised, with mean 1.44 (1.07-2.10). Amongst the parents of the compound heterozygotes, who were not selected for molecular analysis following haematological screening, half of the cases were completely silent. Interaction with severe beta-thalassaemia mutations always resulted in the clinical phenotype of mild non-transfusion-dependent thalassaemia intermedia.
authors.affiliation: First Department of Paediatrics, Athens University, St Sophia's Children's Hospital, Athens, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Maragoudaki
authors.forename: E
authors.initials: E
authors.lastname: Kanavakis
authors.forename: J
authors.initials: J
authors.lastname: Traeger-Synodinos
authors.forename: C
authors.initials: C
authors.lastname: Vrettou
authors.forename: M
authors.initials: M
authors.lastname: Tzetis
authors.forename: A
authors.initials: A
authors.lastname: Metaxotou-Mavrommati
authors.forename: C
authors.initials: C
authors.lastname: Kattamis
mesh_terms: D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics*; D002648:Child; D005260:Female; D005914:Globins / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D017086:beta-Thalassemia / Q000235:genetics*
chemical_list: D005914:Globins