Analysis of platelet membrane glycoprotein polymorphisms in Glanzmann thrombasthenia showed the French gypsy mutation in the αiib gene to be strongly linked to the HPA-1b polymorphism in β3

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 β3, 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 αIIb. Seven of these patients were homozygous for the HPA-1b alloantigen and the other two heterozygous HPA-1a/1b. As the αIIb and β3 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 α2 gene, or in the Kozak or HPA-2 polymorphisms of GPIbα, suggesting that none of these alleles result in increased survival in Glanzmann thrombasthenia. © 2003 International Society on Thrombosis and Haemostasis.