An alpha-thalassemia phenotype in a Dutch Hindustani, caused by a new point mutation that creates an alternative splice donor site in the first exon of the alpha2-globin gene

Hemoglobin. 2004 Aug;28(3):255-9. doi: 10.1081/hem-120040257.

Abstract

The proband is an elderly woman (79 years of age) of Surinamese-Hindustani origin, suspected of being a carrier of a nondeletional alpha-thalassemia (thal) because of a moderate microcytic hypochromic anemia at normal ferritin levels and in the absence of any other alpha-thal deletions. Sequence analysis revealed a silent mutation (GGC-->GGT) at codon 22 of the alpha2-globin gene. This mutation generates a splice donor site consensus sequence (GGTGAG) between codons 22 and 23. The abnormally spliced mRNA leads to a premature termination between codons 48 and 49. The presence of a downstream intron may induce the intracellular degradation of the affected mRNA, a pathway known as nonsense mediated decay (NMD), and this explains the alpha(+)-thal phenotype observed in the patient. The codon 22 (GGC-->GGT) transition described in this report is the first mutation creating a splice donor site in one of the alpha-globin genes.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Anemia, Hypochromic / genetics
  • Codon, Terminator / genetics*
  • Female
  • Humans
  • Peptide Chain Termination, Translational / genetics
  • Point Mutation*
  • RNA Splicing / genetics*
  • RNA Stability / genetics*
  • alpha-Thalassemia / genetics*

Substances

  • Codon, Terminator