title: Molecular, haematological and clinical studies of a silent beta-gene C-->G mutation at 6 bp 3' to the termination codon (+1480 C-->G) in twelve Greek families.
abstract: We report the clinical, haematological, biosynthetic and molecular data of 12 beta-thalassaemia intermedia patients and their heterozygous parents, all of whom carried a rare C-->G mutation at nucleotide position 6 3' to the termination codon (term. cd +6 C-->G) in the 3' untranslated region (3' UTR) of the beta-globin gene (+1480 C-->G). This mutation has been reported previously in a single beta-thalassaemia intermedia patient of Greek origin. The 12 patients of the present study had the clinical phenotype of mild non-transfusion-dependent thalassaemia intermedia, preserving haemoglobin levels around 9 g/dl and haemoglobin F levels <25%. All were compound heterozygotes for the +1480 C-->G mutation and common severe beta-thalassaemia mutations. The haematological parameters of heterozygotes with this mutation were within the normal range with the exception of a slightly raised alpha/non-alpha-globin chain synthesis (1.2-1.9). mRNA analysis demonstrated a 20-34% reduction in mRNA levels associated with the +1480 C-->G mutation compared to normal beta-globin alleles. These findings confirm that the C-->G mutation at position 6 3' to the termination codon is a mild beta-thalassaemia mutation causing slight reduction in beta-globin mRNA levels and beta-globin chain synthesis. It becomes clinically relevant when co-inherited with a severe beta-thalassaemia mutation in trans.
authors.affiliation: First Department of Paediatrics, Athens University, St Sophia's Children's Hospital, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Maragoudaki
authors.forename: C
authors.initials: C
authors.lastname: Vrettou
authors.forename: E
authors.initials: E
authors.lastname: Kanavakis
authors.forename: J
authors.initials: J
authors.lastname: Traeger-Synodinos
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; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000032:analysis; D005914:Globins / Q000235:genetics*; D006115:Greece; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D010375:Pedigree; D011296:Prenatal Diagnosis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D017086:beta-Thalassemia / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D005914:Globins; D004247:DNA