Molecular characterization of a novel 10.3 kb deletion causing beta-thalassaemia with unusually high Hb A2

Br J Haematol. 1992 Dec;82(4):735-44. doi: 10.1111/j.1365-2141.1992.tb06952.x.

Abstract

A family of Asian-Indian descent has a variant form of beta-thalassaemia characterized by unusually high levels of Hb A2 in the heterozygous state. The propositus who is homozygous for the mutation has thalassaemia intermedia. Restriction endonuclease mapping suggested the presence of a 10.3 kilobase (kb) deletion removing the whole of the beta-globin gene. Subsequently, molecular analysis was performed by directly sequencing a specifically amplified region of genomic DNA. A 10329 basepair deletion was precisely defined which results in the loss of the 5' beta promoter region and the entire beta-globin gene. The deletion extends from 3011 bp 5' to the mRNA cap site to an L1 repeat element downstream of the beta-globin gene and is very similar to the 12.6 kb deletion of Dutch beta zero-thalassaemia. In common with four other mutations, both these deletions remove the 5' promoter region of the beta gene and all are associated with unusually elevated levels of Hb A2 in the heterozygous state.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Base Sequence
  • Blotting, Southern
  • Child
  • Child, Preschool
  • Chromosome Deletion*
  • DNA / chemistry
  • Female
  • Globins / genetics*
  • Hemoglobin A2 / analysis*
  • Humans
  • Infant
  • Male
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Restriction Mapping
  • Thalassemia / genetics*

Substances

  • Globins
  • DNA
  • Hemoglobin A2