Identification of the linkage of a 1.357 KB beta-globin gene deletion and A gamma-globin gene triplication in a Chinese family

Hemoglobin. 2010;34(4):343-53. doi: 10.3109/03630269.2010.486357.

Abstract

The 1.357 kb beta-globin gene deletion was identified in a Chinese family by multiplex ligation-dependent probe amplification (MLPA) followed by gap-polymerase chain reaction (gap-PCR) and sequencing. Interestingly, this form of the deletion was linked to a -(G)gamma-(AG)gamma-(A)gamma triplication. The proband, a compound heterozygote for this linked mutant gene and a beta-globin gene [-28 (A>G)] mutation, had a phenotype of beta-thalassemia intermedia (beta-TI). She was not transfusion dependent and had the following parameters: a Hb level of 5.3 g/dL, 72.8% Hb F and 55.1% (G)gamma chain in Hb F. Four members of the family, who were carriers of this linked mutant gene, had a hematological phenotype of beta(0)-thalassemia (beta(0)-thal) with high Hb F and low (G)gamma chain values. RNA analyses showed decreased levels of beta-globin mRNA and increased levels of gamma-globin mRNA in heterozygotes. Haplotype analyses indicated that the unusual form of the beta-globin gene deletion and gamma-globin gene triplication in cis were linked to halotype [+ - - - - - -].

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Child
  • China
  • DNA Mutational Analysis
  • Family Health
  • Female
  • Gene Deletion*
  • Gene Duplication*
  • Genetic Linkage
  • Humans
  • Male
  • Molecular Sequence Data
  • Pedigree
  • Sequence Homology, Nucleic Acid
  • beta-Globins / genetics*
  • beta-Thalassemia / genetics
  • gamma-Globins / genetics*

Substances

  • beta-Globins
  • gamma-Globins