2024-03-28T08:37:19Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/728312020-10-20T13:04:10Zcom_10261_86com_10261_1col_10261_339
DIGITAL.CSIC
author
González-Manchón, Consuelo
author
Butta, Nora
author
Larrucea, Susana
author
García Arias-Salgado, Elena
author
Alonso, Sonia
author
López, Angela
author
Parrilla, Roberto L.
2013-03-25T09:30:20Z
2013-03-25T09:30:20Z
2004-12
Thrombosis and Haemostasis 92(6):1377-1386(2004)
0340-6245
http://hdl.handle.net/10261/72831
10.1160/TH04-06-0380
We report the analysis of a variant case of thrombasthenic phenotypethat is a compound heterozygote for two mutationslocated within the metal ion dependent adhesion site (MIDAS)of the β3 subunit.The patient inherited a maternal allele carryingthe Met124Val substitution and a paternal allele thatchanges Asp119 to Tyr. Phenotyping of the human platelet antigen1 (HPA-1) showed that the platelet αIIbβ3 complex in thepatient was mostly accounted for by the Asp 119Tyr allele thatdoes not bind to fibrinogen (Fg). The patient showed agonistinducedbinding of platelets to Fg but neither binding to PAC-1nor cell aggregation could be detected, most likely due to the minute expression (≤5%) of αIIb(124Val)β3 receptors. CHOcells expressing (124Val)β3 showed a diminished surfaceexpression of aIIbß3, enhanced adhesion to immobilized Fg,and spontaneous aggregation in the presence of soluble Fg, suggestingthat (124Val)β3 may confer constitutive activity to theαIIb(124Val)β3 receptors. A distinct feature of these cells is thefailure of DTT to enhance the binding to soluble Fg and the formationof cell aggregates. The substitution of (124Met)β3 byeither a polar or a positively charged amino acid restored thesurface exposure and function of the αIIbβ3 receptors whereasa negatively charged residue did not
eng
closedAccess
Platelets
αIIbβ3
thrombasthenia
β3 gain function mutation
A variant thrombasthenic phenotype associated with compound heterozygosity of integrin beta3-subunit: (Met124Val)beta3 alters the subunit dimerization rendering a decreased number of constitutive active alphaIIbbeta3 receptors
artículo
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URL
https://digital.csic.es/bitstream/10261/72831/1/restringido.pdf
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restringido.pdf.txt