Analysis of platelet membrane glycoprotein polymorphisms in Glanzmann thrombasthenia showed the French gypsy mutation in the alphaIIb gene to be strongly linked to the HPA-1b polymorphism in beta3

J Thromb Haemost. 2003 Mar;1(3):573-5. doi: 10.1046/j.1538-7836.2003.00107.x.

Abstract

We have tested the DNA of a large series of Glanzmann thrombasthenia patients for polymorphisms in platelet membrane glycoproteins. To our surprise, we noted a high prevalence of the HPA-1b allele of beta3, the minority allele in a normal population. This proved to be due to the presence of nine patients homozygous for the so-called French gypsy mutation (IVS15[ + 1]G-->A) in alphaIIb. Seven of these patients were homozygous for the HPA-1b alloantigen and the other two heterozygous HPA-1a/1b. As the alphaIIb and beta3 genes are both on chromosome 17, it is highly probable that the French gypsy mutation first arose on a chromosome encoding HPA-1b. For other adhesion receptors, no major differences were seen in the distribution of the A1, A2 and A3 alleles in the alpha2 gene, or in the Kozak or HPA-2 polymorphisms of GPIbalpha, suggesting that none of these alleles result in increased survival in Glanzmann thrombasthenia.

MeSH terms

  • Amino Acid Substitution
  • Antigens, Human Platelet / genetics
  • Genetic Linkage*
  • Genetic Testing
  • Genotype
  • Humans
  • Integrin beta3 / genetics
  • Linkage Disequilibrium
  • Mutation, Missense
  • Platelet Membrane Glycoprotein IIb / genetics
  • Platelet Membrane Glycoproteins / genetics*
  • Polymorphism, Genetic*
  • Thrombasthenia / blood
  • Thrombasthenia / genetics*

Substances

  • Antigens, Human Platelet
  • Integrin beta3
  • Platelet Membrane Glycoprotein IIb
  • Platelet Membrane Glycoproteins
  • human platelet antigen 1b