A Novel Frame-shift Mutation Of 540 A Deletion Identified In GPⅡb Gene From A Patient With Glanzmann Thrombasthenia

Glanzmann's thrombasthenia (GT) is a hereditary bleeding function disorder characterized by quantitative or qualitative abnormality of platelet glycoproteinⅡb—Ⅲa receptor(GPⅡb/Ⅲa). GT is classified into three types as follows , typeⅠ, surface expression of GPⅡb/Ⅲa is below 5% of normal expression,and typeⅡ, GPⅡb/Ⅲa expression is in the range of 5-20%,and variant type, which has impaired functions despite normal expression (over 50%) of GPⅡb/Ⅲa.The structure and organization of the GPⅡb and GPⅢa genes is now known . Deletions, insertions and point mutations have been identified in both the GPⅡb and GPⅢa genes of GT patients .100 kinds of gene mutation have been identified in the GPⅡb and GPⅢa genes of GT patients. The majority of these lesions rise to single amino acid substitutions and small deletions.A 3-year-old boy with Glanzmann's thrombasthenia has a bleeding history with purpura and epistaxis. Platelet aggregation was absent by ADP or epinephrine and normal aggregation with ristocetin when compared with normal healthy controls.To elucidate the molecular mechanism of Glanzmann thrombasthenia,We detected a mutation in the GPⅡb gene of the patient with Glanzmann's thrombasthenia with PCR-SSCP assay. Western blotting confirmed absence of GPⅡb and GPⅢa receptor reduced in the patient. The result of PCR-SSCP and direct sequencing showed no abnormalities in the GPⅢa gene, but a deletion of A-base in the band at the site of 540 in GPⅡb gene(540A) was existed . The deletion of A-base at 540 is a cause of GPⅡb development.The data published on journals and Glanzmann thrombasthenia database searching indicated that this deletion was not presented in it. The frame-shift mutation caused by deletion of 540A in GPⅡb gene is a novel mutation which is the genetic defect in the patient with GT.