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

Br J Haematol. 1998 Oct;103(1):45-51. doi: 10.1046/j.1365-2141.1998.00966.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • DNA / analysis
  • Globins / genetics*
  • Greece
  • Heterozygote
  • Humans
  • Mutation*
  • Pedigree
  • Prenatal Diagnosis
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • beta-Thalassemia / genetics*

Substances

  • RNA, Messenger
  • Globins
  • DNA