title: Novel molecular defect in the platelet ADP receptor P2Y12 of a patient with haemorrhagic diathesis.
abstract: BACKGROUND
  The platelet adenosine 5'-diphosphate (ADP) receptor P2Y(12) plays a crucial role in haemostasis. Only a few patients with haemorrhagic diathesis due to molecular defects in the P2Y(12) receptor have been described so far. We report a novel molecular defect in the gene coding for P2Y(12) in a patient with a history of epistaxis, easy bruising and excessive posttraumatic blood loss.
  
  
  METHODS
  Platelet aggregation studies, perfusion studies, in which patient blood was perfused over collagen surfaces at arterial shear rates, and PCR and sequencing were used.
  
  
  RESULTS
  Platelet aggregation studies showed impaired ADP and collagen-induced aggregation for patient G.S. Perfusion of patient blood over collagen surfaces showed small thrombi consisting of spread platelets overlayered with non-spread platelets. These thrombi were identical to control thrombi formed in the presence of a P2Y(12) antagonist. DNA analysis of the P2Y(12) gene revealed a novel heterozygous base pair C-->A substitution in exon 3, changing codon 258 from proline to threonine in the third extracellular loop of the P2Y(12) receptor.
  
  
  CONCLUSIONS
  We conclude that perfusion studies with patient blood are of added value in the diagnostic process, which resulted in identification of a novel molecular defect in the P2Y(12) gene of a patient with haemorrhagic diathesis.
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Isala Klinieken, Zwolle, The Netherlands. jaremijin@gmail.com
authors.forename: Jasper A
authors.initials: JA
authors.lastname: Remijn
authors.forename: Martin J W
authors.initials: MJ
authors.lastname: IJsseldijk
authors.forename: Annuska L M
authors.initials: AL
authors.lastname: Strunk
authors.forename: Andre P
authors.initials: AP
authors.lastname: Abbes
authors.forename: Henk
authors.initials: H
authors.lastname: Engel
authors.forename: Bert
authors.initials: B
authors.lastname: Dikkeschei
authors.forename: Ellen C
authors.initials: EC
authors.lastname: Dompeling
authors.forename: Philip G
authors.initials: PG
authors.lastname: de Groot
authors.forename: Robbert J
authors.initials: RJ
authors.lastname: Slingerland
mesh_terms: D000328:Adult; D001791:Blood Platelet Disorders; D003094:Collagen; D004252:DNA Mutational Analysis; D006474:Hemorrhagic Disorders / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics*; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010477:Perfusion; D010974:Platelet Aggregation; D010979:Platelet Function Tests; D018048:Receptors, Purinergic P2 / Q000172:deficiency / Q000235:genetics*; D058925:Receptors, Purinergic P2Y12
chemical_list: C548576:P2RY12 protein, human; D018048:Receptors, Purinergic P2; D058925:Receptors, Purinergic P2Y12; D003094:Collagen