Bilateral linkage between a new deletion polymorphism in intron 21 of the GP IIb gene and the HPA-3b (Bakb) determinant.

Glycoproteins (GP) IIb (alpha IIb) and GP IIIa (beta 3) form heterodimeric complexes (GP IIb-IIIa) at the platelet surface and mediate platelet aggregation by binding fibrinogen after platelet activation. The structures and DNA sequences of the GP IIb and GP IIIa genes are known. Punctual mutations resulting in alloantigen systems (HPA) have been described on both genes, as have a series of genetic defects giving rise to Glanzmann's thrombasthenia (GT). We now report a nine base pair deletion located in intron 21 of the GP IIb gene. This was found both in unrelated GT patients and in normal individuals. Subsequent studies showed that the deletion polymorphism and the mutation responsible for the platelet alloantigen. HPA-3b, were linked together. The deletion was always present when the gene carried the HPA-3b genotype, but was never observed in association with the HPA-3a polymorphism. Analysis of 60 independent alleles from 30 unrelated caucasian individuals revealed no exceptions to this linkage. It is the first time that two genetic markers have been reported to be linked to each other on the GP IIb gene.