A Cys374Tyr Homozygous Mutation of Platelet Glycoprotein IIIa

A 20-year-old woman from a consanguineous family in the Hunan Province of the People‘s Republic of China was diagnosed as having Glanzmann‘s thrombasthenia based on (1) nearly a lifelong history of epistaxis, gum bleeding, petechiae, and purpura; (2) severe menorrhagia resulting in anemia and need for whole-blood transfusion; (3) normal coagulation assays; (4) prolonged bleeding time; (5) absent clot retraction; (6) decreased glass bead retention; (7) absent platelet aggregation in response to adenine diphosphate, epinephrine, and collagen; and (8) normal initial slope of platelet aggregation in response to ristocetin, but with a diminished maximal extent. The patient’s platelets had a decreased level of platelet fibrinogen, but the deficiency was not as severe as in other Glanzmann’s thrombasthenia patients. As judged by monoclonal antibody binding studies, surface glycoprotein (GP) Ilb/llla ( ( Y ~ @ ~ ) expression was less than 15% of normal and ay& vitronectin receptor expression was 15% to 19k of normal, suggesting that the defect was in GPllla (p3). lmmunoblotting of platelet lysates demonstrated decreased levels of GPllb (-30% to 359/0 of normal) and GPllla