Association of an α-globin gene cluster duplication and heterozygous β-thalassemia in a patient with a severe thalassemia syndrome

Hemoglobin. 2015;39(2):102-6. doi: 10.3109/03630269.2015.1012678. Epub 2015 Feb 18.

Abstract

We describe a new case of a β-thalassemia (β-thal) heterozygote with the mutation IVS-II-654 (C>T) presenting with a transfusion-dependent phenotype. Multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (CGH) analyses of the α-globin gene cluster revealed a full duplication of the α-globin genes including the upstream regulatory element. The duplicated allele and the normal allele in trans resulted in a total of six active α-globin genes. The severe clinical phenotype seemed to be related to the considerable excess of the α- and β-globin deficit caused by the presence of the β-thal. α-Globin cluster duplication should be considered in patients heterozygous for β-thal who show a more severe phenotype than β-thal trait.

Keywords: multiplex ligation-dependent probe amplification (MLPA); α-globin gene duplication; α/β Ratio; β-thalassemia (β-thal).

Publication types

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

MeSH terms

  • Child
  • Chromosomes, Human, Pair 16
  • Comparative Genomic Hybridization
  • DNA Copy Number Variations
  • Erythrocyte Indices
  • Female
  • Gene Duplication*
  • Heterozygote*
  • Humans
  • Introns
  • Multigene Family*
  • Mutation
  • Severity of Illness Index
  • Syndrome
  • Thalassemia / diagnosis*
  • Thalassemia / genetics*
  • alpha-Globins / genetics*
  • beta-Globins / genetics*
  • beta-Thalassemia / genetics*

Substances

  • alpha-Globins
  • beta-Globins