Identification of a new dysfunctional platelet P2Y12 receptor variant associated with bleeding diathesis.

ABSTRACT: Defects of the platelet P2Y12 receptor (P2Y12R) for adenosine diphosphate (ADP) are associated with increased bleeding risk. The study of molecular abnormalities associated with inherited qualitative defects of the P2Y12R protein is useful to unravel structure-function relationships of the receptor. We describe the case of 2 brothers, sons of first cousins, with lifelong history of abnormal bleeding, associated with dysfunctional P2Y12R and a previously undescribed missense mutation in the encoding gene. ADP (4-20 µM)-induced aggregation of patients' platelets was markedly reduced and rapidly reversible. Other agonists induced borderline-normal aggregation. Inhibition of vasodilator-stimulated phosphoprotein phosphorylation and prostaglandin E1-induced increase in cyclic adenosine monophos

SUBMITTER: Lecchi A 

PROVIDER: S-EPMC4319231 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature