SearchPublisher and Institutes
You are here: Home :: Area NEM :: Medical science :: Human medicine
Consuelo Gonzlez-Manchn, Nora Butta, Susana Larrucea, Elena G. Arias-Salgado, Sonia Alonso, Angela Lpez, Roberto Parrilla
A variant thrombasthenic phenotype associated with compound heterozygosity of integrin 3-subunit: (Met124Val)3 alters the subunit dimerization rendering a decreased number of constitutive active Iib3 receptors
We report the analysis of a variant case of thrombasthenic phenotype that is a compound heterozygote for two mutations located within the metal ion dependent adhesion site (MIDAS) of the 3 subunit.The patient inherited a maternal allele carrying the Met124Val substitution and a paternal allele that changes Asp119 to Tyr. Phenotyping of the human platelet antigen 1 (HPA-1) showed that the platelet IIb3 complex in the patient was mostly accounted for by the Asp 119Tyr allele that does not bind to fibrinogen (Fg). The patient showed agonistinduced binding of platelets to Fg but neither binding to PAC-1 nor cell aggregation could be detected, most likely due to the minute expression (5%) of IIb(124Val)3 receptors. CHO cells expressing (124Val)3 showed a diminished surface expression of IIb3, enhanced adhesion to immobilized Fg, and spontaneous aggregation in the presence of soluble Fg, suggesting that (124Val)3 may confer constitutive activity to the IIb(124Val)3 receptors. A distinct feature of these cells is the failure of DTT to enhance the binding to soluble Fg and the formation of cell aggregates. The substitution of (124Met)3 by either a polar or a positively charged amino acid restored the surface exposure and function of the IIb3 receptors whereas a negatively charged residue did not.
Thrombosis and Haemostasis, Schattauer
Print ISSN: 0340-6245
Volume: 92, 12/2004
Pages: 1377 - 1386